545:, as NMNAT enzymes have been shown to prevent SARM1-mediated depletion of NAD. This relationship is further supported by the fact that mice lacking NMNAT2, which are normally not viable, are completely rescued by SARM1 deletion, placing NMNAT2 activity upstream of SARM1. Other pro-degeneration signaling pathways, such as the MAP kinase pathway, have been linked to SARM1 activation. MAPK signaling has been shown to promote the loss of NMNAT2, thereby promoting SARM1 activation, although SARM1 activation also triggers the MAP kinase cascade, indicating some form of feedback loop exists. One explanation for the protective effect of the Wld mutation is that the NMNAT1 region, which is normally localized to the soma, substitutes for the labile survival factor NMNAT2 to prevent SARM1 activation when the N-terminal Ube4 region of the WldS protein localizes it to the axon. The fact that the enhanced survival of Wld axons is due to the slower turnover of Wld compared to NMNAT2 also helps explain why SARM1 knockout confers longer protection, as SARM1 will be completely inactive regardless of inhibitor activity whereas Wld will eventually be degraded. Possibles implications of the SARM1 pathway in regard to human health may be found in animal models which exhibit
128:
the portion of the nerve fiber proximal to the lesion sends out sprouts towards those tubes and these sprouts are attracted by growth factors produced by
Schwann cells in the tubes. If a sprout reaches the tube, it grows into it and advances about 1 mm per day, eventually reaching and reinnervating the target tissue. If the sprouts cannot reach the tube, for instance because the gap is too wide or scar tissue has formed, surgery can help to guide the sprouts into the tubes. Regeneration is efficient in the PNS, with near complete recovery in case of lesions that occur close to the distal nerve terminal. However recovery is hardly observed at all in the
32:
303:
attributed to the ErbB2 receptors and the ErbB3 receptors. This proliferation could further enhance the myelin cleaning rates and plays an essential role in regeneration of axons observed in PNS. Schwann cells emit growth factors that attract new axonal sprouts growing from the proximal stump after complete degeneration of the injured distal stump. This leads to possible reinnervation of the target cell or organ. However, the reinnervation is not necessarily perfect, as possible misleading occurs during reinnervation of the proximal axons to target cells.
57:
371:(NGF) is produced in very small amounts. However, upon injury, NGF mRNA expression increases by five to seven-fold within a period of 14 days. Nerve fibroblasts and Schwann cells play an important role in increased expression of NGF mRNA. Macrophages also stimulate Schwann cells and fibroblasts to produce NGF via macrophage-derived interleukin-1. Other neurotrophic molecules produced by Schwann cells and fibroblasts together include
283:
source of macrophage recruitment factors is serum. Delayed macrophage recruitment was observed in B-cell deficient mice lacking serum antibodies. These signaling molecules together cause an influx of macrophages, which peaks during the third week after injury. While
Schwann cells mediate the initial stage of myelin debris clean up, macrophages come in to finish the job. Macrophages are facilitated by
112:(CNS). It occurs in the section of the axon distal to the site of injury and usually begins within 24–36 hours of a lesion. Prior to degeneration, the distal section of the axon tends to remain electrically excitable. After injury, the axonal skeleton disintegrates, and the axonal membrane breaks apart. Axonal degeneration is followed by degradation of the
177:(the part nearer the cell body) and distal ends within 30 minutes of injury. After separation, dystrophic bulb structures form at both terminals and the transected membranes are sealed. A brief latency phase occurs in the distal segment during which it remains electrically excitable and structurally intact. Degeneration follows with swelling of the
355:
almost absent in most vertebrate species. The primary cause for this could be the delay in clearing up myelin debris. Myelin debris, present in CNS or PNS, contains several inhibitory factors. The prolonged presence of myelin debris in CNS could possibly hinder the regeneration. An experiment conducted on
483:
mutated mice, macrophage infiltration was considerably delayed by up to six to eight days. However, once the axonal degradation has begun, degeneration takes its normal course, and, respective of the nervous system, degradation follows at the above-described rates. Possible effects of this late onset
446:
Although the protein created localizes within the nucleus and is barely detectable in axons, studies suggest that its protective effect is due to its presence in axonal and terminal compartments. The protection provided by the Wld protein is intrinsic to the neurons and not surrounding support cells,
2018:
Mack TG, Reiner M, Beirowski B, Mi W, Emanuelli M, Wagner D, Thomson D, Gillingwater T, Court F, Conforti L, Fernando FS, Tarlton A, Andressen C, Addicks K, Magni G, Ribchester RR, Perry VH, Coleman MP (December 2001). "Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat
160:
nerves. He then observed the distal nerves from the site of injury, which were separated from their cell bodies in the brain stem. Waller described the disintegration of myelin, which he referred to as "medulla", into separate particles of various sizes. The degenerating axons formed droplets that
469:
synthesis. This in turn activates SIRT1-dependent process within the nucleus, causing changes in gene transcription. NAD by itself may provide added axonal protection by increasing the axon's energy resources. More recent work, however, raises doubt that either NMNAT1 or NAD can substitute for the
319:
were found for up to 22 months. Therefore, CNS rates of myelin sheath clearance are very slow and could possibly be the cause for hindrance in the regeneration capabilities of the CNS axons as no growth factors are available to attract the proximal axons. Another feature that results eventually is
318:
Experiments in
Wallerian degeneration have shown that upon injury oligodendrocytes either undergo programmed cell death or enter a state of rest. Therefore, unlike Schwann cells, oligodendrocytes fail to clean up the myelin sheaths and their debris. In experiments conducted on rats, myelin sheaths
216:
proteases (caused by influx of calcium ion), suggesting that axonal degeneration is an active process and not a passive one as previously misunderstood. Thus the axon undergoes complete fragmentation. The rate of degradation is dependent on the type of injury and is also slower in the CNS than in
127:
Schwann cells respond to loss of axons by extrusion of their myelin sheaths, downregulation of myelin genes, dedifferentiation and proliferation. They finally align in tubes (Büngner bands) and express surface molecules that guide regenerating fibers. Within 4 days of the injury, the distal end of
399:
within the basal laminar tube. Axons have been observed to regenerate in close association to these cells. Schwann cells upregulate the production of cell surface adhesion molecule ninjurin further promoting growth. These lines of cell guide the axon regeneration in proper direction. The possible
282:
of axonal injury. The recruitment of macrophages helps improve the clearing rate of myelin debris. The resident macrophages present in the nerves release further chemokines and cytokines to attract further macrophages. The degenerating nerve also produce macrophage chemotactic molecules. Another
354:
Regeneration follows degeneration. Regeneration is rapid in PNS, allowing for rates of up to 1 millimeter a day of regrowth. Grafts may also be needed to allow for appropriate reinnervation. It is supported by
Schwann cells through growth factors release. CNS regeneration is much slower, and is
302:
Murinson et al. (2005) observed that non-myelinated or myelinated
Schwann cells in contact with an injured axon enter cell cycle thus leading to proliferation. Observed time duration for Schwann cell divisions were approximately 3 days after injury. Possible sources of proliferation signal are
236:
in the CNS. Myelin clearance is the next step in
Wallerian degeneration following axonal degeneration. The cleaning up of myelin debris is different for PNS and CNS. PNS is much faster and efficient at clearing myelin debris in comparison to CNS, and Schwann cells are the primary cause of this
474:
gene. These authors demonstrated by both in vitro and in vivo methods that the protective effect of overexpression of NMNAT1 or the addition of NAD did not protect axons from degeneration. However, later studies showed that NMNAT1 is protective when combined with an axonal targeting peptide,
338:(MHC) class I and II during Wallerian degeneration. The rate of clearance is very slow among microglia in comparison to macrophages. Possible source for variations in clearance rates could include lack of opsonin activity around microglia, and the lack of increased permeability in the
395:. These factors together create a favorable environment for axonal growth and regeneration. Apart from growth factors, Schwann cells also provide structural guidance to further enhance regeneration. During their proliferation phase, Schwann cells begin to form a line of cells called
533:
having intrinsic NAD cleavage activity. The SARM1 protein has four domains, a mitochondrial localization signal, an auto-inhibitory N-terminus region consisting of armadillo/HEAT motifs, two sterile alpha motifs responsible for multimerization, and a C-terminus
460:
mutation slows down the macrophage infiltration, but recent studies suggest that the mutation protects axons rather than slowing down the macrophages. The process by which the axonal protection is achieved is poorly understood. However, studies suggest that the
39:
Fluorescent micrographs (100x) of
Wallerian degeneration in cut and crushed peripheral nerves. Left column is proximal to the injury, right is distal. A and B: 37 hours post cut. C and D: 40 hours post crush. E and F: 42 hours post cut. G and H: 44 hours post
2433:
Osterloh JM, Yang J, Rooney TM, Fox AN, Adalbert R, Powell EH, Sheehan AE, Avery MA, Hackett R, Logan MA, MacDonald JM, Ziegenfuss JS, Milde S, Hou YJ, Nathan C, Ding A, Brown RH, Conforti L, Coleman M, Tessier-Lavigne M, Züchner S, Freeman MR (July 2012).
2346:
Fujiki M, Zhang Z, Guth L, Steward O (July 1996). "Genetic influences on cellular reactions to spinal cord injury: activation of macrophages/microglia and astrocytes is delayed in mice carrying a mutation (WldS) that causes delayed
Wallerian degeneration".
237:
difference. Another key aspect is the change in permeability of the blood-tissue barrier in the two systems. In PNS, the permeability increases throughout the distal stump, but the barrier disruption in CNS is limited to just the site of injury.
266:
extracellular myelin and attract macrophages to myelin debris for further phagocytosis. However, the macrophages are not attracted to the region for the first few days; hence the
Schwann cells take the major role in myelin cleaning until then.
185:. The process takes roughly 24 hours in the PNS, and longer in the CNS. The signaling pathways leading to axolemma degeneration are currently poorly understood. However, research has shown that this AAD process is calcium–independent.
503:
The
Wallerian degeneration pathway has been further illuminated by the discovery that sterile alpha and TIR motif containing 1 (SARM1) protein plays a central role in the Wallerian degeneration pathway. The gene was first identified in a
418:
have delayed Wallerian degeneration, and, thus, allow for the study of the roles of various cell types and the underlying cellular and molecular processes. Current understanding of the process has been possible via experimentation on the
345:
These findings have suggested that the delay in Wallerian degeneration in CNS in comparison to PNS is caused not due to a delay in axonal degeneration, but rather is due to the difference in clearance rates of myelin in CNS and PNS.
1889:
Perry, V. H., Lunn, E. R., Brown, M. C., Cahusac, S. and Gordon, S. (1990), Evidence that the Rate of Wallerian Degeneration is Controlled by a Single Autosomal Dominant Gene. European Journal of Neuroscience, 2: 408-413.
478:
The provided axonal protection delays the onset of Wallerian degeneration. Schwann cell activation should therefore be delayed, as they would not detect axonal degradation signals from ErbB2 receptors. In experiments on
359:, animals that have fast CNS axon regeneration capabilities, found that Wallerian degeneration of an optic nerve injury took up to 10 to 14 days on average, further suggesting that slow clearance inhibits regeneration.
488:
mice, but this is likely a result of the environment being unfavorable for regeneration due to the continued existence of the undegenerated distal fiber, whereas normally debris is cleared, making way for new growth.
2975:
257:
mechanism of Schwann cells is yet to be fully understood. The 'sensing' is followed by decreased synthesis of myelin lipids and eventually stops within 48 hrs. The myelin sheaths separate from the axons at the
334:, and fail to transform into fully phagocytic cells. Those microglia that do transform, clear out the debris effectively. Differentiating phagocytic microglia can be accomplished by testing for expression of
455:
The mutation causes no harm to the mouse. The only known effect is that the Wallerian degeneration is delayed by up to three weeks on average after injury of a nerve. At first, it was suspected that the
330:
play a vital role in CNS Wallerian degeneration. However, their recruitment is slower in comparison to macrophage recruitment in PNS by approximately 3 days. Further, microglia might be activated but
311:
In comparison to Schwann cells, oligodendrocytes require axon signals to survive. In their developmental stages, oligodendrocytes that fail to make contact to axon and receive axon signals undergo
217:
the PNS. Another factor that affects degradation rate is the diameter of the axon: larger axons require a longer time for the cytoskeleton to degrade and thus take a longer time to degenerate.
81:'s cell body) degenerates. A related process of dying back or retrograde degeneration known as 'Wallerian-like degeneration' occurs in many neurodegenerative diseases, especially those where
2164:
Adalbert R, Nógrádi A, Szabó A, Coleman MP (October 2006). "The slow Wallerian degeneration gene in vivo protects motor axons but not their cell bodies after avulsion and neonatal axotomy".
1475:
Koshinaga M, Whittemore SR (April 1995). "The temporal and spatial activation of microglia in fiber tracts undergoing anterograde and retrograde degeneration following spinal cord lesion".
475:
suggesting that the key to the protection provided by Wld was the combination of NMNAT1's activity and the axonal localization provided by the N-terminal domain of the chimeric protein.
800:"Experiments on the Section of the Glossopharyngeal and Hypoglossal Nerves of the Frog, and Observations of the Alterations Produced Thereby in the Structure of Their Primitive Fibres"
553:
deletions in addition to Wld show decreased axonal damage following injury. Specific mutations in NMNAT2 have linked the Wallerian degeneration mechanism to two neurological diseases.
431:
mutation occurring in the mouse chromosome 4. The gene mutation is an 85-kb tandem triplication, occurring naturally. The mutated region contains two associated genes:
2121:
Glass JD, Brushart TM, George EB, Griffin JW (May 1993). "Prolonged survival of transected nerve fibres in C57BL/Ola mice is an intrinsic characteristic of the axon".
1343:
Liu HM, Yang LH, Yang YJ (July 1995). "Schwann cell properties: 3. C-fos expression, bFGF production, phagocytosis and proliferation during Wallerian degeneration".
1847:
Perry VH, Brown MC, Tsao JW (1 October 1992). "The Effectiveness of the Gene Which Slows the Rate of Wallerian Degeneration in C57BL/Ola Mice Declines With Age".
262:
first and then rapidly deteriorate and shorten to form bead-like structures. Schwann cells continue to clear up the myelin debris by degrading their own myelin,
249:
are believed to be responsible for the rapid activation. They activate ErbB2 receptors in the Schwann cell microvilli, which results in the activation of the
2390:
Brown MC, Perry VH, Hunt SP, Lapper SR (March 1994). "Further studies on motor and sensory nerve regeneration in mice with delayed Wallerian degeneration".
173:
influx signaling to promote resealing of severed parts, axonal injuries initially lead to acute axonal degeneration (AAD), which is rapid separation of the
3467:
3041:
960:
Kerschensteiner M, Schwab ME, Lichtman JW, Misgeld T (May 2005). "In vivo imaging of axonal degeneration and regeneration in the injured spinal cord".
568:
326:
Oligodendrocytes fail to recruit macrophages for debris removal. Macrophage entry in general into CNS site of injury is very slow. In contrast to PNS,
529:
levels in the distal section of the injured axon, which then undergoes degeneration. This collapse in NAD levels was later shown to be due to SARM1's
443:
is also part of the mutation. The protective effect of the Wld protein has been shown to be due to the NMNAT1 region's NAD synthesizing active site.
2256:
Conforti L, Fang G, Beirowski B, Wang MS, Sorci L, Asress S, Adalbert R, Silva A, Bridge K, Huang XP, Magni G, Glass JD, Coleman MP (January 2007).
245:
The response of Schwann cells to axonal injury is rapid. The time period of response is estimated to be prior to the onset of axonal degeneration.
510:
mutagenesis screen, and subsequently knockouts of its homologue in mice showed robust protection of transected axons comparable to that of Wld.
1619:
Turner JE, Glaze KA (March 1977). "The early stages of Wallerian degeneration in the severed optic nerve of the newt (Triturus viridescens)".
1512:"Delayed macrophage responses and myelin clearance during Wallerian degeneration in the central nervous system: the dorsal radiculotomy model"
538:
that possesses enzymatic activity. Activation of SARM1 is sufficient to collapse NAD levels and initiate the Wallerian degeneration pathway.
750:
376:
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occurs and is soon followed by degradation of the neurofilaments and other cytoskeleton components. The disintegration is dependent on
1967:
Araki T, Sasaki Y, Milbrandt J (August 2004). "Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration".
447:
and is only locally protective of the axon, indicating an intracellular pathway is responsible for mediating Wallerian degeneration.
628:
3034:
632:
3501:
1755:
Thomas PK, King RH (October 1974). "The degeneration of unmyelinated axons following nerve section: an ultrastructural study".
174:
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strain of mice. The mutation occurred first in mice in Harlan-Olac, a laboratory producing animals the United Kingdom. The
1247:"Complement depletion reduces macrophage infiltration and ctivation during Wallerian degeneration and axonal regeneration"
2072:
Beirowski B, Babetto E, Gilley J, Mazzola F, Conforti L, Janeckova L, Magni G, Ribchester RR, Coleman MP (January 2009).
3027:
2907:"Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1"
598:
1716:"Interleukin 1 increases stability and transcription of mRNA encoding nerve growth factor in cultured rat fibroblasts"
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3199:
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Yang J, Wu Z, Renier N, Simon DJ, Uryu K, Park DS, Greer PA, Tournier C, Davis RJ, Tessier-Lavigne M (January 2015).
526:
518:
466:
372:
3402:
3082:
335:
250:
1296:"Degeneration of myelinated efferent fibers prompts mitosis in Remak Schwann cells of uninjured C-fiber afferents"
3437:
3153:
2546:
2856:"MAPK signaling promotes axonal degeneration by speeding the turnover of the axonal maintenance factor NMNAT2"
1389:, Jacobson MD, Schmid R, Sendtner M, Raff MC (August 1993). "Does oligodendrocyte survival depend on axons?".
400:
source of error that could result from this is possible mismatching of the target cells as discussed earlier.
2297:
Babetto E, Beirowski B, Janeckova L, Brown R, Gilley J, Thomson D, Ribchester RR, Coleman MP (October 2010).
2258:"NAD(+) and axon degeneration revisited: Nmnat1 cannot substitute for Wld(S) to delay Wallerian degeneration"
535:
530:
86:
522:
3340:
3335:
608:
380:
259:
1664:"Changes of nerve growth factor synthesis in nonneuronal cells in response to sciatic nerve transection"
1005:"Endocytotic formation of vesicles and other membranous structures induced by Ca2+ and axolemmal injury"
844:
Coleman MP, Conforti L, Buckmaster EA, Tarlton A, Ewing RM, Brown MC, Lyon MF, Perry VH (August 1998).
603:
388:
384:
132:. One crucial difference is that in the CNS, including the spinal cord, myelin sheaths are produced by
228:
is a phospholipid membrane that wraps around axons to provide them with insulation. It is produced by
31:
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are weaker regenerative abilities in the mice. Studies indicate that regeneration may be impaired in
105:
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56:
3513:
3387:
3013:
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342:. The decreased permeability could further hinder macrophage infiltration to the site of injury.
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97:
studies suggest that a failure to deliver sufficient quantities of the essential axonal protein
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1800:"Ninjurin, a novel adhesion molecule, is induced by nerve injury and promotes axonal growth"
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3288:
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2447:
2074:"Non-nuclear Wld(S) determines its neuroprotective efficacy for axons and synapses in vivo"
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degrades and mitochondria swell up and eventually disintegrate. The depolymerization of
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1980:
1920:
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Due to lack of such favorable promoting factors in CNS, regeneration is stunted in CNS.
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2855:
2831:
2807:"Pathological axonal death through a MAPK cascade that triggers a local energy deficit"
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2299:"Targeting NMNAT1 to axons and synapses transforms its neuroprotective potency in vivo"
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He Z, Koprivica V (21 July 2004). "The Nogo signaling pathway for regeneration block".
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could be stained, thus allowing for studies of the course of individual nerve fibres.
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Walker LJ, Summers DW, Sasaki Y, Brace EJ, Milbrandt J, DiAntonio A (January 2017).
2542:"Resolving the topological enigma in Ca 2+ signaling by cyclic ADP-ribose and NAADP"
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2004:
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695:"Endogenous Nmnat2 is an essential survival factor for maintenance of healthy axons"
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The activity of SARM1 helps to explain the protective nature of the survival factor
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1905:"A gene affecting Wallerian nerve degeneration maps distally on mouse chromosome 4"
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2436:"dSarm/Sarm1 is required for activation of an injury-induced axon death pathway"
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Essuman K, Summers DW, Sasaki Y, Mao X, DiAntonio A, Milbrandt J (March 2017).
1909:
Proceedings of the National Academy of Sciences of the United States of America
1432:
Ludwin SK (31 May 1990). "Oligodendrocyte survival in Wallerian degeneration".
850:
Proceedings of the National Academy of Sciences of the United States of America
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2560:
846:"An 85-kb tandem triplication in the slow Wallerian degeneration (Wlds) mouse"
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299:. However, only complement has shown to help in myelin debris phagocytosis.
229:
121:
2621:
2459:
1988:
1929:
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formation. This further hinders chances for regeneration and reinnervation.
287:, which label debris for removal. The 3 major groups found in serum include
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10.1002/(SICI)1096-9861(19960729)371:3<469::AID-CNE9>3.0.CO;2-0
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905:"Nerve injury, axonal degeneration and neural regeneration: basic insights"
816:
799:
781:
730:
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2598:"SARM1 activation triggers axon degeneration locally via NAD⁺ destruction"
2411:
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2209:"A local mechanism mediates NAD-dependent protection of axon degeneration"
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1948:
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1038:
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Eddleman CS, Ballinger ML, Smyers ME, Fishman HM, Bittner GD (June 1998).
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occurs after axolemma degradation. Early changes include accumulation of
3472:
3070:
2493:"Sarm1-mediated axon degeneration requires both SAM and TIR interactions"
1640:
563:
411:
331:
246:
205:
129:
70:
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2723:
2491:
Gerdts J, Summers DW, Sasaki Y, DiAntonio A, Milbrandt J (August 2013).
1903:
Lyon MF, Ogunkolade BW, Brown MC, Atherton DJ, Perry VH (October 1993).
746:"NMNAT: It's an NAD + Synthase… It's a Chaperone… It's a Neuroprotector"
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2134:
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1445:
1386:
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1058:"Axon degeneration: molecular mechanisms of a self-destruction pathway"
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mutation leads to increased NMNAT1 activity, which leads to increased
440:
320:
296:
292:
117:
2705:
Sasaki Y, Nakagawa T, Mao X, DiAntonio A, Milbrandt J (October 2016).
2207:
Wang J, Zhai Q, Chen Y, Lin E, Gu W, McBurney MW, He Z (August 2005).
1245:
Dailey AT, Vellino AM, Benthem L, Silver J, Kliot M (September 1998).
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Schwann cells have been observed to recruit macrophages by release of
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Gerdts J, Brace EJ, Sasaki Y, DiAntonio A, Milbrandt J (April 2015).
327:
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2658:"+ Cleavage Activity that Promotes Pathological Axonal Degeneration"
2041:
1198:"Microanatomy of axon/glial signaling during Wallerian degeneration"
1120:(1 July 2007). "Why is Wallerian degeneration in the CNS so slow?".
959:
1157:"Multiple forms of Ca-activated protease from rat brain and muscle"
973:
284:
271:
178:
2758:"S, Confers Lifelong Rescue in a Mouse Model of Severe Axonopathy"
2032:
362:
3065:
213:
170:
843:
3108:
3092:
2979:
1661:
1196:
Guertin AD, Zhang DP, Mak KS, Alberta JA, Kim HA (March 2005).
542:
432:
225:
113:
98:
78:
3280:
2296:
1714:
Lindholm D, Heumann R, Hengerer B, Thoenen H (November 1988).
1713:
1002:
104:
Wallerian degeneration occurs after axonal injury in both the
77:
distal to the injury (which in most cases is farther from the
3087:
2071:
498:
436:
188:
Granular disintegration of the axonal cytoskeleton and inner
2490:
1385:
2163:
1902:
1662:
Heumann R, Korsching S, Bandtlow C, Thoenen H (June 1987).
356:
149:
74:
2704:
2595:
2120:
1294:
Murinson BB, Archer DR, Li Y, Griffin JW (February 2005).
1244:
2255:
804:
Philosophical Transactions of the Royal Society of London
69:
is an active process of degeneration that results when a
2853:
525:. SARM1 activation locally triggers a rapid collapse of
2755:
2655:
1293:
253:(MAPK). Although MAPK activity is observed, the injury
2345:
1195:
2651:
2649:
2432:
2017:
3049:
2957:
2756:
Gilley J, Ribchester RR, Coleman MP (October 2017).
2389:
1966:
1345:
Journal of Neuropathology and Experimental Neurology
3468:
Spinal cord injury without radiographic abnormality
1474:
1154:
124:, serve to clear the debris from the degeneration.
2646:
1892:https://doi.org/10.1111/j.1460-9568.1990.tb00433.x
569:Connective tissue in the peripheral nervous system
2804:
1051:
433:nicotinamide mononucleotide adenylyltransferase 1
3536:
743:
513:SARM1 catalyzes the synthesis and hydrolysis of
2206:
1962:
1960:
1958:
1111:
1109:
1107:
1105:
1103:
1101:
450:
363:Schwann cells and endoneural fibroblasts in PNS
1846:
1797:
643:
406:
3296:
3035:
2591:
2589:
2200:
1561:Neuroscience: Fundamentals for Rehabilitation
1509:
839:
837:
835:
751:Current Opinion in Genetics & Development
692:
2533:
2249:
2011:
1955:
1840:
1577:
1379:
1287:
1189:
1115:
1098:
181:, and eventually the formation of bead-like
2339:
1791:
1748:
1707:
1655:
1618:
1583:
1558:
1503:
1468:
1425:
1342:
1336:
1238:
1148:
953:
902:
737:
686:
646:"Wallerian degeneration, wld(s), and nmnat"
637:
377:glial cell line-derived neurotrophic factor
3303:
3289:
3042:
3028:
2586:
1754:
1612:
1155:Zimmerman UP, Schlaepfer WW (March 1984).
832:
55:
3012:at the U.S. National Library of Medicine
2932:
2922:
2904:
2881:
2871:
2830:
2781:
2732:
2722:
2681:
2629:
2569:
2559:
2516:
2467:
2322:
2273:
2232:
2097:
2040:
1938:
1928:
1815:
1731:
1690:
1527:
1319:
1270:
1221:
1172:
1081:
1028:
928:
879:
869:
815:
771:
744:Brazill JM, Li C, Zhu Y, Zhai RG (2017).
720:
710:
669:
169:Although most injury responses include a
16:Biological process of axonal degeneration
2539:
633:University of California, San Francisco
3537:
1598:10.1146/annurev.neuro.27.070203.144340
1431:
1134:10.1146/annurev.neuro.30.051606.094354
797:
644:Coleman MP, Freeman MR (1 June 2010).
164:
144:Wallerian degeneration is named after
73:is cut or crushed and the part of the
3284:
3023:
1510:George R, Griffin JW (October 1994).
793:
791:
693:Gilley J, Coleman MP (January 2010).
439:(UBE4B). A linker region encoding 18
2392:The European Journal of Neuroscience
2349:The Journal of Comparative Neurology
2166:The European Journal of Neuroscience
1849:The European Journal of Neuroscience
1798:Araki T, Milbrandt J (August 1996).
1720:The Journal of Biological Chemistry
1161:The Journal of Biological Chemistry
662:10.1146/annurev-neuro-060909-153248
306:
240:
220:
13:
2404:10.1111/j.1460-9568.1994.tb00285.x
1861:10.1111/j.1460-9568.1992.tb00126.x
1263:10.1523/JNEUROSCI.18-17-06713.1998
1021:10.1523/JNEUROSCI.18-11-04029.1998
921:10.1111/j.1750-3639.1999.tb00229.x
788:
599:Primary and secondary brain injury
120:. The macrophages, accompanied by
14:
3556:
2953:
2905:Henninger N, et al. (2016).
903:Stoll G, Müller HW (April 1999).
629:Trauma and Wallerian Degeneration
373:brain-derived neurotrophic factor
3403:Chronic traumatic encephalopathy
3083:Lateralization of brain function
2178:10.1111/j.1460-9568.2006.05103.x
1357:10.1097/00005072-199507000-00002
336:major histocompatibility complex
251:mitogen-activated protein kinase
30:
3438:Anterior spinal artery syndrome
3310:
3154:Somatosensory evoked potentials
2898:
2847:
2798:
2749:
2698:
2547:Journal of Biological Chemistry
2484:
2426:
2383:
2290:
2157:
2114:
2065:
1896:
1883:
1552:
1045:
349:
2509:10.1523/JNEUROSCI.1197-13.2013
2315:10.1523/JNEUROSCI.1189-10.2010
2262:Cell Death and Differentiation
2090:10.1523/JNEUROSCI.3814-08.2009
1312:10.1523/JNEUROSCI.1372-04.2005
1214:10.1523/JNEUROSCI.3766-04.2005
996:
896:
622:
414:belonging to the strain C57BL/
1:
1817:10.1016/S0896-6273(00)80166-X
1733:10.1016/S0021-9258(18)37599-9
1586:Annual Review of Neuroscience
1174:10.1016/S0021-9258(17)43282-0
1122:Annual Review of Neuroscience
650:Annual Review of Neuroscience
615:
87:amyotrophic lateral sclerosis
2774:10.1016/j.celrep.2017.09.027
2674:10.1016/j.neuron.2017.02.022
1403:10.1016/0960-9822(93)90039-Q
712:10.1371/journal.pbio.1000300
7:
3341:Intraventricular hemorrhage
3336:Intraparenchymal hemorrhage
2497:The Journal of Neuroscience
2303:The Journal of Neuroscience
2213:The Journal of Cell Biology
2078:The Journal of Neuroscience
1671:The Journal of Cell Biology
1300:The Journal of Neuroscience
1251:The Journal of Neuroscience
1202:The Journal of Neuroscience
1062:The Journal of Cell Biology
1009:The Journal of Neuroscience
798:Waller A (1 January 1850).
609:Spinal cord injury research
556:
536:Toll/Interleukin-1 receptor
451:Effects of the Wld mutation
407:Wallerian degeneration slow
381:ciliary neurotrophic factor
260:Schmidt-Lanterman incisures
152:in 1850, by severing their
101:is a key initiating event.
10:
3561:
2823:10.1016/j.cell.2014.11.053
1563:(3rd ed.). Saunders.
496:
389:insulin-like growth factor
385:leukemia inhibitory factor
139:
136:and not by Schwann cells.
3514:Injury of accessory nerve
3482:
3428:
3318:
3258:
3215:
3167:
3149:Auditory evoked potential
3129:
3122:
3101:
3058:
2961:
2561:10.1074/jbc.REV119.009635
764:10.1016/j.gde.2017.03.014
437:ubiquitination factor e4b
148:. Waller experimented on
106:peripheral nervous system
44:
38:
29:
24:
3388:Post-concussion syndrome
3014:Medical Subject Headings
2540:Lee HC, Zhao YJ (2019).
2123:Journal of Neurocytology
1757:Journal of Neurocytology
549:, as mice which contain
492:
393:fibroblast growth factor
200:at the site of injury.
3497:Peripheral nerve injury
3463:Posterior cord syndrome
3420:Penetrating head injury
3361:Subarachnoid hemorrhage
3328:Intracranial hemorrhage
3159:Visual evoked potential
2622:10.1126/science.1258366
2460:10.1126/science.1223899
1989:10.1126/science.1098014
1930:10.1073/pnas.90.20.9717
1489:10.1089/neu.1995.12.209
871:10.1073/pnas.95.17.9985
604:Seddon's classification
594:Peripheral nerve injury
507:Drosophila melanogaster
3519:Brachial plexus injury
3509:Wallerian degeneration
3443:Brown-Séquard syndrome
3393:Second-impact syndrome
3320:Traumatic brain injury
3243:Long-term potentiation
3195:Postsynaptic potential
3139:Bereitschaftspotential
3010:Wallerian+Degeneration
2275:10.1038/sj.cdd.4401944
1683:10.1083/jcb.104.6.1623
1559:Lundy-Ekman L (2007).
1529:10.1006/exnr.1994.1164
1516:Experimental Neurology
1477:Journal of Neurotrauma
817:10.1098/rstl.1850.0021
547:traumatic brain injury
146:Augustus Volney Waller
110:central nervous system
67:Wallerian degeneration
3453:Central cord syndrome
3448:Cauda equina syndrome
3410:Diffuse axonal injury
3078:Intracranial pressure
2225:10.1083/jcb.200504028
1633:10.1002/ar.1091870303
1621:The Anatomical Record
1434:Acta Neuropathologica
1074:10.1083/jcb.201108111
1052:Wang JT, Medress ZA,
574:Diffuse axonal injury
202:Endoplasmic reticulum
3398:Dementia pugilistica
3248:Long-term depression
3223:Axoplasmic transport
2924:10.1093/brain/aww001
116:and infiltration by
85:is impaired such as
3415:Abusive head trauma
3378:Cerebral laceration
3238:Synaptic plasticity
3230:/Nerve regeneration
2873:10.7554/eLife.22540
2724:10.7554/eLife.19749
2668:(6): 1334–1343.e5.
2614:2015Sci...348..453G
2554:(52): 19831–19843.
2452:2012Sci...337..481O
2021:Nature Neuroscience
1981:2004Sci...305.1010A
1921:1993PNAS...90.9717L
862:1998PNAS...95.9985C
369:nerve growth factor
367:In healthy nerves,
340:blood–brain barrier
232:in the PNS, and by
165:Axonal degeneration
91:Alzheimer's disease
3430:Spinal cord injury
3373:Cerebral contusion
3185:Membrane potential
3050:Physiology of the
2135:10.1007/BF01195555
1769:10.1007/BF01098736
1446:10.1007/BF00308922
579:Digestion chambers
429:autosomal-dominant
3532:
3531:
3524:Traumatic neuroma
3484:Peripheral nerves
3356:Epidural hematoma
3351:Subdural hematoma
3278:
3277:
3274:
3273:
3228:Neuroregeneration
3175:Neurotransmission
3005:
3004:
2309:(40): 13291–304.
1570:978-1-4160-2578-8
589:Neuroregeneration
515:cyclic ADP-ribose
198:paranodal regions
64:
63:
19:Medical condition
3552:
3368:Brain herniation
3305:
3298:
3291:
3282:
3281:
3190:Action potential
3168:Other short term
3131:Evoked potential
3127:
3126:
3044:
3037:
3030:
3021:
3020:
2959:
2958:
2947:
2946:
2936:
2926:
2917:(4): 1094–1105.
2902:
2896:
2895:
2885:
2875:
2851:
2845:
2844:
2834:
2802:
2796:
2795:
2785:
2753:
2747:
2746:
2736:
2726:
2702:
2696:
2695:
2685:
2653:
2644:
2643:
2633:
2593:
2584:
2583:
2573:
2563:
2537:
2531:
2530:
2520:
2503:(33): 13569–80.
2488:
2482:
2481:
2471:
2430:
2424:
2423:
2387:
2381:
2380:
2343:
2337:
2336:
2326:
2294:
2288:
2287:
2277:
2253:
2247:
2246:
2236:
2204:
2198:
2197:
2161:
2155:
2154:
2118:
2112:
2111:
2101:
2069:
2063:
2062:
2044:
2027:(12): 1199–206.
2019:chimeric gene".
2015:
2009:
2008:
1975:(5686): 1010–3.
1964:
1953:
1952:
1942:
1932:
1900:
1894:
1887:
1881:
1880:
1844:
1838:
1837:
1819:
1795:
1789:
1788:
1752:
1746:
1745:
1735:
1726:(31): 16348–51.
1711:
1705:
1704:
1694:
1668:
1659:
1653:
1652:
1616:
1610:
1609:
1581:
1575:
1574:
1556:
1550:
1549:
1531:
1507:
1501:
1500:
1472:
1466:
1465:
1429:
1423:
1422:
1383:
1377:
1376:
1340:
1334:
1333:
1323:
1291:
1285:
1284:
1274:
1242:
1236:
1235:
1225:
1193:
1187:
1186:
1176:
1152:
1146:
1145:
1113:
1096:
1095:
1085:
1056:(January 2012).
1049:
1043:
1042:
1032:
1000:
994:
993:
957:
951:
950:
932:
900:
894:
893:
883:
873:
841:
830:
829:
819:
795:
786:
785:
775:
741:
735:
734:
724:
714:
690:
684:
683:
673:
641:
635:
626:
397:Bands of Bungner
307:Clearance in CNS
241:Clearance in PNS
234:oligodendrocytes
221:Myelin clearance
183:axonal spheroids
154:glossopharyngeal
134:oligodendrocytes
83:axonal transport
60:
59:
34:
22:
21:
3560:
3559:
3555:
3554:
3553:
3551:
3550:
3549:
3535:
3534:
3533:
3528:
3478:
3424:
3314:
3309:
3279:
3270:
3254:
3234:Neuroplasticity
3211:
3163:
3118:
3097:
3054:
3048:
3006:
3001:
3000:
2970:
2956:
2951:
2950:
2903:
2899:
2852:
2848:
2817:(1–2): 161–76.
2803:
2799:
2754:
2750:
2703:
2699:
2654:
2647:
2608:(6233): 453–7.
2594:
2587:
2538:
2534:
2489:
2485:
2446:(6093): 481–4.
2431:
2427:
2388:
2384:
2344:
2340:
2295:
2291:
2254:
2250:
2205:
2201:
2162:
2158:
2119:
2115:
2070:
2066:
2016:
2012:
1965:
1956:
1915:(20): 9717–20.
1901:
1897:
1888:
1884:
1845:
1841:
1796:
1792:
1753:
1749:
1712:
1708:
1666:
1660:
1656:
1617:
1613:
1582:
1578:
1571:
1557:
1553:
1508:
1504:
1473:
1469:
1430:
1426:
1391:Current Biology
1384:
1380:
1341:
1337:
1292:
1288:
1257:(17): 6713–22.
1243:
1239:
1208:(13): 3478–87.
1194:
1190:
1153:
1149:
1114:
1099:
1050:
1046:
1015:(11): 4029–41.
1001:
997:
962:Nature Medicine
958:
954:
909:Brain Pathology
901:
897:
856:(17): 9985–90.
842:
833:
796:
789:
742:
738:
705:(1): e1000300.
691:
687:
642:
638:
627:
623:
618:
613:
559:
501:
495:
453:
427:mutation is an
409:
365:
352:
309:
243:
223:
167:
142:
95:Primary culture
54:
20:
17:
12:
11:
5:
3558:
3548:
3547:
3530:
3529:
3527:
3526:
3521:
3516:
3511:
3506:
3505:
3504:
3502:classification
3499:
3488:
3486:
3480:
3479:
3477:
3476:
3475:(Quadriplegia)
3470:
3465:
3460:
3455:
3450:
3445:
3440:
3434:
3432:
3426:
3425:
3423:
3422:
3417:
3412:
3407:
3406:
3405:
3400:
3395:
3390:
3380:
3375:
3370:
3365:
3364:
3363:
3358:
3353:
3345:
3344:
3343:
3338:
3330:
3324:
3322:
3316:
3315:
3308:
3307:
3300:
3293:
3285:
3276:
3275:
3272:
3271:
3269:
3268:
3266:Myelinogenesis
3262:
3260:
3256:
3255:
3253:
3252:
3251:
3250:
3245:
3231:
3225:
3219:
3217:
3213:
3212:
3210:
3209:
3208:
3207:
3202:
3192:
3187:
3182:
3177:
3171:
3169:
3165:
3164:
3162:
3161:
3156:
3151:
3146:
3141:
3135:
3133:
3124:
3120:
3119:
3117:
3116:
3111:
3105:
3103:
3099:
3098:
3096:
3095:
3090:
3085:
3080:
3075:
3074:
3073:
3062:
3060:
3056:
3055:
3052:nervous system
3047:
3046:
3039:
3032:
3024:
3018:
3017:
3003:
3002:
2999:
2998:
2987:
2971:
2966:
2965:
2963:
2962:Classification
2955:
2954:External links
2952:
2949:
2948:
2897:
2846:
2797:
2748:
2697:
2645:
2585:
2532:
2483:
2425:
2382:
2338:
2289:
2248:
2199:
2156:
2113:
2064:
2010:
1954:
1895:
1882:
1855:(10): 1000–2.
1839:
1790:
1763:(4): 497–512.
1747:
1706:
1677:(6): 1623–31.
1654:
1627:(3): 291–310.
1611:
1576:
1569:
1551:
1502:
1467:
1424:
1378:
1335:
1306:(5): 1179–87.
1286:
1237:
1188:
1147:
1097:
1044:
995:
974:10.1038/nm1229
952:
895:
831:
787:
736:
685:
636:
620:
619:
617:
614:
612:
611:
606:
601:
596:
591:
586:
581:
576:
571:
566:
560:
558:
555:
497:Main article:
494:
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408:
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36:
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27:
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9:
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3408:
3404:
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3346:
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3337:
3334:
3333:
3331:
3329:
3326:
3325:
3323:
3321:
3317:
3313:
3306:
3301:
3299:
3294:
3292:
3287:
3286:
3283:
3267:
3264:
3263:
3261:
3257:
3249:
3246:
3244:
3241:
3240:
3239:
3235:
3232:
3229:
3226:
3224:
3221:
3220:
3218:
3214:
3206:
3203:
3201:
3198:
3197:
3196:
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3183:
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3155:
3152:
3150:
3147:
3145:
3142:
3140:
3137:
3136:
3134:
3132:
3128:
3125:
3121:
3115:
3112:
3110:
3107:
3106:
3104:
3102:Primarily PNS
3100:
3094:
3091:
3089:
3086:
3084:
3081:
3079:
3076:
3072:
3069:
3068:
3067:
3064:
3063:
3061:
3059:Primarily CNS
3057:
3053:
3045:
3040:
3038:
3033:
3031:
3026:
3025:
3022:
3015:
3011:
3008:
3007:
2997:
2993:
2992:
2988:
2986:
2982:
2981:
2977:
2973:
2972:
2969:
2964:
2960:
2944:
2940:
2935:
2930:
2925:
2920:
2916:
2912:
2908:
2901:
2893:
2889:
2884:
2879:
2874:
2869:
2865:
2861:
2857:
2850:
2842:
2838:
2833:
2828:
2824:
2820:
2816:
2812:
2808:
2801:
2793:
2789:
2784:
2779:
2775:
2771:
2767:
2763:
2759:
2752:
2744:
2740:
2735:
2730:
2725:
2720:
2716:
2712:
2708:
2707:"+ depletion"
2701:
2693:
2689:
2684:
2679:
2675:
2671:
2667:
2663:
2659:
2652:
2650:
2641:
2637:
2632:
2627:
2623:
2619:
2615:
2611:
2607:
2603:
2599:
2592:
2590:
2581:
2577:
2572:
2567:
2562:
2557:
2553:
2549:
2548:
2543:
2536:
2528:
2524:
2519:
2514:
2510:
2506:
2502:
2498:
2494:
2487:
2479:
2475:
2470:
2465:
2461:
2457:
2453:
2449:
2445:
2441:
2437:
2429:
2421:
2417:
2413:
2409:
2405:
2401:
2397:
2393:
2386:
2378:
2374:
2370:
2366:
2362:
2358:
2355:(3): 469–84.
2354:
2350:
2342:
2334:
2330:
2325:
2320:
2316:
2312:
2308:
2304:
2300:
2293:
2285:
2281:
2276:
2271:
2268:(1): 116–27.
2267:
2263:
2259:
2252:
2244:
2240:
2235:
2230:
2226:
2222:
2219:(3): 349–55.
2218:
2214:
2210:
2203:
2195:
2191:
2187:
2183:
2179:
2175:
2172:(8): 2163–8.
2171:
2167:
2160:
2152:
2148:
2144:
2140:
2136:
2132:
2129:(5): 311–21.
2128:
2124:
2117:
2109:
2105:
2100:
2095:
2091:
2087:
2084:(3): 653–68.
2083:
2079:
2075:
2068:
2060:
2056:
2052:
2048:
2043:
2038:
2034:
2033:10.1038/nn770
2030:
2026:
2022:
2014:
2006:
2002:
1998:
1994:
1990:
1986:
1982:
1978:
1974:
1970:
1963:
1961:
1959:
1950:
1946:
1941:
1936:
1931:
1926:
1922:
1918:
1914:
1910:
1906:
1899:
1893:
1886:
1878:
1874:
1870:
1866:
1862:
1858:
1854:
1850:
1843:
1835:
1831:
1827:
1823:
1818:
1813:
1810:(2): 353–61.
1809:
1805:
1801:
1794:
1786:
1782:
1778:
1774:
1770:
1766:
1762:
1758:
1751:
1743:
1739:
1734:
1729:
1725:
1721:
1717:
1710:
1702:
1698:
1693:
1688:
1684:
1680:
1676:
1672:
1665:
1658:
1650:
1646:
1642:
1638:
1634:
1630:
1626:
1622:
1615:
1607:
1603:
1599:
1595:
1592:(1): 341–68.
1591:
1587:
1580:
1572:
1566:
1562:
1555:
1547:
1543:
1539:
1535:
1530:
1525:
1522:(2): 225–36.
1521:
1517:
1513:
1506:
1498:
1494:
1490:
1486:
1483:(2): 209–22.
1482:
1478:
1471:
1463:
1459:
1455:
1451:
1447:
1443:
1440:(2): 184–91.
1439:
1435:
1428:
1420:
1416:
1412:
1408:
1404:
1400:
1397:(8): 489–97.
1396:
1392:
1388:
1382:
1374:
1370:
1366:
1362:
1358:
1354:
1351:(4): 487–96.
1350:
1346:
1339:
1331:
1327:
1322:
1317:
1313:
1309:
1305:
1301:
1297:
1290:
1282:
1278:
1273:
1268:
1264:
1260:
1256:
1252:
1248:
1241:
1233:
1229:
1224:
1219:
1215:
1211:
1207:
1203:
1199:
1192:
1184:
1180:
1175:
1170:
1167:(5): 3210–8.
1166:
1162:
1158:
1151:
1143:
1139:
1135:
1131:
1128:(1): 153–79.
1127:
1123:
1119:
1112:
1110:
1108:
1106:
1104:
1102:
1093:
1089:
1084:
1079:
1075:
1071:
1067:
1063:
1059:
1055:
1048:
1040:
1036:
1031:
1026:
1022:
1018:
1014:
1010:
1006:
999:
991:
987:
983:
979:
975:
971:
967:
963:
956:
948:
944:
940:
936:
931:
926:
922:
918:
915:(2): 313–25.
914:
910:
906:
899:
891:
887:
882:
877:
872:
867:
863:
859:
855:
851:
847:
840:
838:
836:
827:
823:
818:
813:
809:
805:
801:
794:
792:
783:
779:
774:
769:
765:
761:
757:
753:
752:
747:
740:
732:
728:
723:
718:
713:
708:
704:
700:
696:
689:
681:
677:
672:
667:
663:
659:
656:(1): 245–67.
655:
651:
647:
640:
634:
630:
625:
621:
610:
607:
605:
602:
600:
597:
595:
592:
590:
587:
585:
582:
580:
577:
575:
572:
570:
567:
565:
562:
561:
554:
552:
548:
544:
539:
537:
532:
528:
524:
520:
517:(cADPR) from
516:
511:
509:
508:
500:
490:
487:
482:
476:
473:
468:
464:
459:
448:
444:
442:
438:
435:(NMNAT1) and
434:
430:
426:
422:
417:
413:
404:
401:
398:
394:
390:
386:
382:
378:
374:
370:
360:
358:
347:
343:
341:
337:
333:
329:
324:
322:
316:
314:
304:
300:
298:
294:
290:
286:
281:
277:
273:
268:
265:
261:
256:
252:
248:
238:
235:
231:
230:Schwann cells
227:
218:
215:
211:
207:
203:
199:
195:
191:
186:
184:
180:
176:
172:
162:
159:
155:
151:
147:
137:
135:
131:
125:
123:
122:Schwann cells
119:
115:
114:myelin sheath
111:
107:
102:
100:
96:
92:
88:
84:
80:
76:
72:
68:
58:
52:
49:
47:
43:
37:
33:
28:
23:
3508:
3492:Nerve injury
3347:Extra-axial
3332:Intra-axial
2989:
2974:
2914:
2910:
2900:
2863:
2859:
2849:
2814:
2810:
2800:
2768:(1): 10–16.
2765:
2762:Cell Reports
2761:
2751:
2714:
2710:
2700:
2665:
2661:
2605:
2601:
2551:
2545:
2535:
2500:
2496:
2486:
2443:
2439:
2428:
2398:(3): 420–8.
2395:
2391:
2385:
2352:
2348:
2341:
2306:
2302:
2292:
2265:
2261:
2251:
2216:
2212:
2202:
2169:
2165:
2159:
2126:
2122:
2116:
2081:
2077:
2067:
2024:
2020:
2013:
1972:
1968:
1912:
1908:
1898:
1885:
1852:
1848:
1842:
1807:
1803:
1793:
1760:
1756:
1750:
1723:
1719:
1709:
1674:
1670:
1657:
1624:
1620:
1614:
1589:
1585:
1579:
1560:
1554:
1519:
1515:
1505:
1480:
1476:
1470:
1437:
1433:
1427:
1394:
1390:
1381:
1348:
1344:
1338:
1303:
1299:
1289:
1254:
1250:
1240:
1205:
1201:
1191:
1164:
1160:
1150:
1125:
1121:
1065:
1061:
1047:
1012:
1008:
998:
968:(5): 572–7.
965:
961:
955:
912:
908:
898:
853:
849:
807:
803:
755:
749:
739:
702:
699:PLOS Biology
698:
688:
653:
649:
639:
624:
584:Nerve injury
550:
540:
512:
505:
502:
485:
480:
477:
471:
470:full length
462:
457:
454:
445:
424:
420:
415:
410:
402:
396:
366:
353:
350:Regeneration
344:
325:
317:
310:
301:
279:
269:
254:
244:
224:
206:microtubules
194:mitochondria
187:
168:
143:
126:
103:
66:
65:
25:Nerve injury
3545:Neurotrauma
3473:Tetraplegia
3312:Neurotrauma
3071:Wakefulness
1116:Vargas ME,
1068:(1): 7–18.
810:: 423–429.
758:: 156–162.
564:Axonotmesis
441:amino acids
332:hypertrophy
264:phagocytose
247:Neuregulins
158:hypoglossal
130:spinal cord
118:macrophages
71:nerve fiber
3458:Paraplegia
3383:Concussion
3205:Inhibitory
3200:Excitatory
616:References
531:TIR domain
523:ADP-ribose
321:glial scar
297:antibodies
293:pentraxins
289:complement
276:chemokines
190:organelles
108:(PNS) and
89:(ALS) and
3216:Long term
3180:Chronaxie
3114:Sensation
1387:Barres BA
1118:Barres BA
1054:Barres BA
328:microglia
313:apoptosis
272:cytokines
210:ubiquitin
51:Neurology
46:Specialty
3539:Category
2943:26912636
2892:28095293
2841:25594179
2792:28978465
2743:27735788
2692:28334607
2640:25908823
2580:31672920
2527:23946415
2478:22678360
2420:37501852
2333:20926655
2284:16645633
2243:16043516
2194:25359698
2186:17074042
2151:45871975
2108:19158292
2051:11770485
2042:1842/737
2005:32370137
1997:15310905
1877:24786532
1869:12106435
1834:12471778
1785:37385200
1606:15217336
1546:40089749
1462:36103242
1419:39909326
1411:15335686
1373:25055891
1330:15689554
1232:15800203
1142:17506644
1092:22232700
990:25287010
982:15821747
947:24140507
939:10219748
782:28445802
731:20126265
680:20345246
557:See also
285:opsonins
179:axolemma
175:proximal
3066:Arousal
2996:D014855
2934:5006226
2883:5241118
2832:4306654
2783:5640801
2734:5063586
2683:6284238
2631:4513950
2610:Bibcode
2602:Science
2571:6937575
2518:3742939
2469:5225956
2448:Bibcode
2440:Science
2412:8019679
2377:8797673
2369:8842900
2324:6634738
2234:2171458
2143:8315413
2099:6665162
2059:8316115
1977:Bibcode
1969:Science
1949:8415768
1917:Bibcode
1826:8780658
1777:4436692
1742:3263368
1701:3034917
1692:2114490
1649:2028827
1538:7957737
1497:7629867
1454:1697140
1365:7602323
1321:6725954
1281:9712643
1272:6792968
1223:6724908
1183:6321500
1083:3255986
1039:9592084
1030:6792792
930:8098499
890:9707587
858:Bibcode
773:5515290
722:2811159
671:5223592
280:sensing
255:sensing
214:calpain
196:in the
171:calcium
140:History
3109:Reflex
3093:Memory
3016:(MeSH)
2941:
2931:
2890:
2880:
2839:
2829:
2790:
2780:
2741:
2731:
2690:
2680:
2662:Neuron
2638:
2628:
2578:
2568:
2525:
2515:
2476:
2466:
2418:
2410:
2375:
2367:
2331:
2321:
2282:
2241:
2231:
2192:
2184:
2149:
2141:
2106:
2096:
2057:
2049:
2003:
1995:
1947:
1937:
1875:
1867:
1832:
1824:
1804:Neuron
1783:
1775:
1740:
1699:
1689:
1647:
1641:851236
1639:
1604:
1567:
1544:
1536:
1495:
1460:
1452:
1417:
1409:
1371:
1363:
1328:
1318:
1279:
1269:
1230:
1220:
1181:
1140:
1090:
1080:
1037:
1027:
988:
980:
945:
937:
927:
888:
878:
826:108444
824:
780:
770:
729:
719:
678:
668:
543:NMNAT2
391:, and
295:, and
278:after
226:Myelin
99:NMNAT2
79:neuron
53:
40:crush.
3259:Other
3088:Sleep
2985:G58.8
2911:Brain
2860:eLife
2711:eLife
2416:S2CID
2373:S2CID
2190:S2CID
2147:S2CID
2055:S2CID
2001:S2CID
1940:47641
1873:S2CID
1830:S2CID
1781:S2CID
1667:(PDF)
1645:S2CID
1542:S2CID
1458:S2CID
1415:S2CID
1369:S2CID
986:S2CID
943:S2CID
881:21448
822:JSTOR
551:Sarm1
499:SARM1
493:SARM1
357:newts
150:frogs
3144:P300
3123:Both
2991:MeSH
2939:PMID
2888:PMID
2837:PMID
2811:Cell
2788:PMID
2739:PMID
2688:PMID
2636:PMID
2576:PMID
2523:PMID
2474:PMID
2408:PMID
2365:PMID
2329:PMID
2280:PMID
2239:PMID
2182:PMID
2139:PMID
2104:PMID
2047:PMID
1993:PMID
1945:PMID
1865:PMID
1822:PMID
1773:PMID
1738:PMID
1697:PMID
1637:PMID
1602:PMID
1565:ISBN
1534:PMID
1493:PMID
1450:PMID
1407:PMID
1361:PMID
1326:PMID
1277:PMID
1228:PMID
1179:PMID
1138:PMID
1088:PMID
1035:PMID
978:PMID
935:PMID
886:PMID
778:PMID
727:PMID
676:PMID
412:Mice
274:and
212:and
156:and
75:axon
2976:ICD
2929:PMC
2919:doi
2915:139
2878:PMC
2868:doi
2827:PMC
2819:doi
2815:160
2778:PMC
2770:doi
2729:PMC
2719:doi
2678:PMC
2670:doi
2626:PMC
2618:doi
2606:348
2566:PMC
2556:doi
2552:294
2513:PMC
2505:doi
2464:PMC
2456:doi
2444:337
2400:doi
2357:doi
2353:371
2319:PMC
2311:doi
2270:doi
2229:PMC
2221:doi
2217:170
2174:doi
2131:doi
2094:PMC
2086:doi
2037:hdl
2029:doi
1985:doi
1973:305
1935:PMC
1925:doi
1857:doi
1812:doi
1765:doi
1728:doi
1724:263
1687:PMC
1679:doi
1675:104
1629:doi
1625:187
1594:doi
1524:doi
1520:129
1485:doi
1442:doi
1399:doi
1353:doi
1316:PMC
1308:doi
1267:PMC
1259:doi
1218:PMC
1210:doi
1169:doi
1165:259
1130:doi
1078:PMC
1070:doi
1066:196
1025:PMC
1017:doi
970:doi
925:PMC
917:doi
876:PMC
866:doi
812:doi
808:140
768:PMC
760:doi
717:PMC
707:doi
666:PMC
658:doi
527:NAD
521:to
519:NAD
486:Wld
481:Wld
472:Wld
467:NAD
463:Wld
458:Wld
425:Wld
421:Wld
416:Wld
3541::
2994::
2983::
2980:10
2937:.
2927:.
2913:.
2909:.
2886:.
2876:.
2866:.
2862:.
2858:.
2835:.
2825:.
2813:.
2809:.
2786:.
2776:.
2766:21
2764:.
2760:.
2737:.
2727:.
2717:.
2713:.
2709:.
2686:.
2676:.
2666:93
2664:.
2660:.
2648:^
2634:.
2624:.
2616:.
2604:.
2600:.
2588:^
2574:.
2564:.
2550:.
2544:.
2521:.
2511:.
2501:33
2499:.
2495:.
2472:.
2462:.
2454:.
2442:.
2438:.
2414:.
2406:.
2394:.
2371:.
2363:.
2351:.
2327:.
2317:.
2307:30
2305:.
2301:.
2278:.
2266:14
2264:.
2260:.
2237:.
2227:.
2215:.
2211:.
2188:.
2180:.
2170:24
2168:.
2145:.
2137:.
2127:22
2125:.
2102:.
2092:.
2082:29
2080:.
2076:.
2053:.
2045:.
2035:.
2023:.
1999:.
1991:.
1983:.
1971:.
1957:^
1943:.
1933:.
1923:.
1913:90
1911:.
1907:.
1871:.
1863:.
1851:.
1828:.
1820:.
1808:17
1806:.
1802:.
1779:.
1771:.
1759:.
1736:.
1722:.
1718:.
1695:.
1685:.
1673:.
1669:.
1643:.
1635:.
1623:.
1600:.
1590:27
1588:.
1540:.
1532:.
1518:.
1514:.
1491:.
1481:12
1479:.
1456:.
1448:.
1438:80
1436:.
1413:.
1405:.
1393:.
1367:.
1359:.
1349:54
1347:.
1324:.
1314:.
1304:25
1302:.
1298:.
1275:.
1265:.
1255:18
1253:.
1249:.
1226:.
1216:.
1206:25
1204:.
1200:.
1177:.
1163:.
1159:.
1136:.
1126:30
1124:.
1100:^
1086:.
1076:.
1064:.
1060:.
1033:.
1023:.
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