Axon degeneration and regeneration: Insights from drosophila models of nerve injury

Annual Review of Cell and Developmental Biology

Volumn 28, Issue , 2012, Pages 575-597

  Fang, Yanshan ^a   Bonini, Nancy M ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

axon regrowth; axotomy; neuroprotection; Wallerian degeneration; WldS

Indexed keywords

AMYLOID PRECURSOR PROTEIN; CYCLIC AMP; CYCLIC AMP DEPENDENT PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 9; PROTEASOME; UBIQUITIN;

AXONAL INJURY; CELL DEATH; CYTOSKELETON; DEGENERATIVE DISEASE; DROSOPHILA MELANOGASTER; EXPLANT; FORELIMB; GLIA; HUMAN; LARVA; MICROTUBULE; NERVE FIBER DEGENERATION; NERVE FIBER REGENERATION; NERVE FIBER TRANSECTION; NERVE FIBER TRANSPORT; NERVE INJURY; NERVOUS SYSTEM INJURY; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; OLFACTORY SYSTEM; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SPINAL CORD INJURY; SPINAL GANGLION; TRAUMATIC BRAIN INJURY;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; AXONS; CRANIAL NERVE INJURIES; DISEASE MODELS, ANIMAL; DROSOPHILA; DROSOPHILA PROTEINS; HUMANS; NERVE DEGENERATION; NERVE REGENERATION; SIGNAL TRANSDUCTION;

DROSOPHILA MELANOGASTER; WALLERIA;

EID: 84870192151     PISSN: 10810706     EISSN: 15308995     Source Type: Book Series    
DOI: 10.1146/annurev-cellbio-101011-155836     Document Type: Review

References (155)

1. Adachi-Yamada T, Fujimura-Kamada K, Nishida Y, Matsumoto K. 1999. Distortion of proximodistal information causes JNK-dependent apoptosis in Drosophila wing. Nature 400:166-69
2. Ali YO, McCormack R, Darr A, Zhai RG. 2011. Nicotinamide mononucleotide adenylyltransferase is a stress response protein regulated by the heat shock factor/hypoxia-inducible factor 1 αpathway. J. Biol. Chem. 286:19089-99
3. Ali YO, Ruan K, Zhai RG. 2012. NMNAT suppresses Tau-induced neurodegeneration by promoting clearance of hyperphosphorylated Tau oligomers in a Drosophila model of tauopathy. Hum. Mol. Genet. 21:237-50
4. Ambegaokar SS, Roy B, JacksonGR. 2010. Neurodegenerative models in Drosophila: polyglutamine disorders, Parkinson disease, and amyotrophic lateral sclerosis. Neurobiol. Dis. 40:29-39
5. Antenor-Dorsey JAV, O'Malley K. 2012. WldS but not Nmnat1 protects dopaminergic neurites from MPP+ neurotoxicity. Mol. Neurodegener. 7:5
6. Araki T, Sasaki Y, Milbrandt J. 2004. Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science 305:1010-13
7. Avery MA, Rooney TM, Pandya JD, Wishart TM, Gillingwater TH, et al. 2012. WldS prevents axon degeneration through increased mitochondrial flux and enhanced mitochondrial Ca2+ buffering. Curr. Biol. 22:596-600
8. Avery MA, Sheehan AE, Kerr KS, Wang J, Freeman MR. 2009. WldS requires Nmnat1 enzymatic activity and N16-VCP interactions to suppressWallerian degeneration. J. Cell Biol. 184:501-13
9. Ayaz D, Leyssen M, Koch M, Yan J, Srahna M, et al. 2008. Axonal injury and regeneration in the adult brain of Drosophila. J. Neurosci. 28:6010-21
10. Babetto E, Beirowski B, Janeckova L, Brown R, Gilley J, et al. 2010. Targeting NMNAT1 to axons and synapses transforms its neuroprotective potency in vivo. J. Neurosci. 30:13291-304
11. Banerjee S, Pillai AM, Paik R, Li J, Bhat MA. 2006. Axonal ensheathment and septate junction formation in the peripheral nervous system of Drosophila. J. Neurosci. 26:3319-29
12. Beirowski B, Babetto E, Gilley J, Mazzola F, Conforti L, et al. 2009. Non-nuclear WldS determines its neuroprotective efficacy for axons and synapses in vivo. J. Neurosci. 29:653-68
13. Bejjani RE, Hammarlund M. 2012. Notch signaling inhibits axon regeneration. Neuron 26:268-78
14. Bellen HJ, Lu Y, Beckstead R, Bhat MA. 1998. Neurexin IV, caspr and paranodin-novel members of the neurexin family: encounters of axons and glia. Trends Neurosci. 21:444-49
15. Bernier B, Castejon S, Culver DG, Glass JD. 1999. Axonal neurofilaments are resistant to calpain-mediated degradation in the WLDS mouse. Neuroreport 10:1423-26
16. Bier E. 2005. Drosophila, the golden bug, emerges as a tool for human genetics. Nat. Rev. Genet. 6:9-23
17. Bradke F, Fawcett JW, SpiraME. 2012. Assembly of a new growth cone after axotomy: the precursor to axon regeneration. Nat. Rev. Neurosci. 13:183-93
18. Brochtrup A, Hummel T. 2010. Olfactory map formation in the Drosophila brain: genetic specificity and neuronal variability. Curr. Opin. Neurobiol. 21:85-92
19. Carmine-Simmen K, Proctor T, Tschape J, Poeck B, Triphan T, et al. 2009. Neurotoxic effects induced by the Drosophila amyloid-βpeptide suggest a conserved toxic function. Neurobiol. Dis. 33:274-81
20. Cavalli V, Kujala P, Klumperman J, Goldstein LS. 2005. Sunday Driver links axonal transport to damage signaling. J. Cell Biol. 168:775-87
21. Chen L, Chisholm AD. 2011. Axon regeneration mechanisms: insights from C. elegans. Trends Cell Biol. 21:577-84
22. Chen L, Wang Z, Ghosh-Roy A, Hubert T, Yan D, et al. 2011. Axon regeneration pathways identified by systematic genetic screening in C. elegans. Neuron 71:1043-57
23. Chiu H, Alqadah A, Chuang CF, Chang C. 2011. C. elegans as a genetic model to identify novel cellular and molecular mechanisms underlying nervous system regeneration. Cell Adhes. Migr. 5:387-94
24. ColemanM. 2005. Axon degeneration mechanisms: commonality amid diversity. Nat. Rev. Neurosci. 6:889-98
25. ColemanMP, Freeman MR. 2010. Wallerian degeneration,WldS, and Nmnat. Annu. Rev. Neurosci. 33:245-67
26. Collins CA, Wairkar YP, Johnson SL, DiAntonio A. 2006. Highwire restrains synaptic growth by attenuating a MAP kinase signal. Neuron 51:57-69
27. Conde C, Caceres A. 2009. Microtubule assembly, organization and dynamics in axons and dendrites. Nat. Rev. Neurosci. 10:319-32
28. Conforti L, Fang G, Beirowski B, Wang MS, Sorci L, et al. 2007. NAD+ and axon degeneration revisited: Nmnat1 cannot substitute forWldS to delay Wallerian degeneration. Cell Death Differ. 14:116-27
29. Conforti L, Janeckova L, Wagner D, Mazzola F, Cialabrini L, et al. 2011. Reducing expression of NAD+ synthesizing enzyme NMNAT1 does not affect the rate of Wallerian degeneration. FEBS J. 278:2666-79
30. Conforti L, Tarlton A, Mack TG, Mi W, Buckmaster EA, et al. 2000. A Ufd2/D4Cole1e chimeric protein and overexpression of Rbp7 in the slowWallerian degeneration (WldS) mouse. Proc. Natl. Acad. Sci. USA 97:11377-82
31. Conforti L, Wilbrey A, Morreale G, Janeckova L, Beirowski B, et al. 2009. WldS protein requires Nmnat activity and a short N-terminal sequence to protect axons in mice. J. Cell Biol. 184:491-500
32. Crocker A, Sehgal A. 2010. Genetic analysis of sleep. Genes Dev. 24:1220-35
33. Doherty J, Logan MA, Tas?demir OE, Freeman MR. 2009. Ensheathing glia function as phagocytes in the adult Drosophila brain. J. Neurosci. 29:4768-81
34. Fang Y, Soares L, Teng X, Geary M, Bonini NM. 2012. A novel Drosophila model of nerve injury reveals an essential role of Nmnat in maintaining axonal integrity. Curr. Biol. 22:590-95
35. Feng Y, Yan T,He Z, ZhaiQ. 2010. WldS,Nmnats and axon degeneration-progress in the past two decades. Protein Cell 1:237-45
36. Ferri A, Sanes JR, ColemanMP, Cunningham JM, Kato AC. 2003. Inhibiting axon degeneration and synapse loss attenuates apoptosis and disease progression in a mouse model of motoneuron disease. Curr. Biol. 13:669-73
37. Fiala A. 2007. Olfaction and olfactory learning in Drosophila: recent progress. Curr. Opin. Neurobiol. 17:720-26
38. Freeman MR, Delrow J, Kim J, Johnson E, Doe CQ. 2003. Unwrapping glial biology: Gcm target genes regulating glial development, diversification, and function. Neuron 38:567-80
39. Freeman MR, Doherty J. 2006. Glial cell biology in Drosophila and vertebrates. Trends Neurosci. 29:82-90
40. Gallo KA, Johnson GL. 2002. Mixed-lineage kinase control of JNK and p38 MAPK pathways. Nat. Rev. Mol. Cell Biol. 3:663-72
41. Garc?a-Alonso LA. 1999. Postembryonic sensory axon guidance in Drosophila. Cell. Mol. Life Sci. 55:1386-98
42. Gelderblom M, Eminel S, Herdegen T, Waetzig V. 2004. c-jun N-terminal kinases ( JNKs) and the cytoskeleton-functions beyond neurodegeneration. Int. J. Dev. Neurosci. 22:559-64
43. Gerits N, Kostenko S, Shiryaev A, JohannessenM,Moens U. 2008. Relations between the mitogen-activated protein kinase and the cAMP-dependent protein kinase pathways: comradeship and hostility. Cell Signal. 20:1592-607
44. Ghannad-Rezaie M, Wang X, Mishra B, Collins C, Chronis N. 2012. Microfluidic chips for in vivo imaging of cellular responses to neural injury in Drosophila larvae. PLoS ONE. 7:e29869
45. Ghosh AS, Wang B, Pozniak CD, Chen M, Watts RJ, Lewcock JW. 2011. DLK induces developmental neuronal degeneration via selective regulation of proapoptotic JNK activity. J. Cell Biol. 194:751-64
46. Ghosh-Roy A, Wu Z, Goncharov A, Jin Y, Chisholm AD. 2010. Calcium and cyclic AMP promote axonal regeneration in Caenorhabditis elegans and require DLK-1 kinase. J. Neurosci. 30:3175-83
47. Gilley J, Coleman MP. 2010. Endogenous Nmnat2 is an essential survival factor for maintenance of healthy axons. PLoS Biol. 8:e1000300
48. Glass JD, Brushart TM, George EB, Griffin JW. 1993. Prolonged survival of transected nerve fibres in C57BL/Ola mice is an intrinsic characteristic of the axon. J. Neurocytol. 22:311-21
49. Glater EE, Megeath LJ, Stowers RS, Schwarz TL. 2006. Axonal transport of mitochondria requires milton to recruit kinesin heavy chain and is light chain independent. J. Cell Biol. 173:545-57
50. Glenner GG, Wong CW. 1984. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 120:885-90
51. G orska-Andrzejak J, Stowers RS, Borycz J, Kostyleva R, Schwarz TL, Meinertzhagen IA. 2003. Mitochondria are redistributed in Drosophila photoreceptors lacking Milton, a kinesin-associated protein. J. Comp. Neurol. 463:372-88
52. Guarnieri DJ, Heberlein U. 2003. Drosophila melanogaster, a genetic model system for alcohol research. Int. Rev. Neurobiol. 54:199-228
53. Hammarlund M, Nix P, Hauth L, Jorgensen EM, Bastiani M. 2009. Axon regeneration requires a conserved MAP kinase pathway. Science 323:802-6
54. Hannila SS, Filbin MT. 2008. The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury. Exp. Neurol. 209:321-32
55. HilliardMA. 2009. Axonal degeneration and regeneration: amechanistic tug-of-war. J. Neurochem. 108:23-32
56. Hoogenraad CC, Bradke F. 2009. Control of neuronal polarity and plasticity-a renaissance for microtubules? Trends Cell Biol. 19:669-76
57. Hoopfer ED, McLaughlin T, Watts RJ, Schuldiner O, O'Leary DDM, Luo L. 2006. WldS protection distinguishes axon degeneration following injury from naturally occurring developmental pruning. Neuron 50:883-95
58. Hoopfer ED, Penton A,Watts RJ, Luo L. 2008. Genomic analysis of Drosophila neuronal remodeling: a role for the RNA-binding protein boule as a negative regulator of axon pruning. J. Neurosci. 28:6092-103
59. Hur E-M, Saijilafu, Zhou FQ. 2011. Growing the growth cone: remodeling the cytoskeleton to promote axon regeneration. Trends Neurosci. 35:164-74
60. Ikonomovic MD, Uryu K, Abrahamson EE, Ciallella JR, Trojanowski JQ, et al. 2004. Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury. Exp. Neurol. 190:192-203
61. ImaiT, SakanoH,Vosshall LB. 2010. Topographicmapping-the olfactory system. Cold Spring Harb. Perspect. Biol. 2:a001776
62. InoueM,Zhai H, SakazakiH,FuruyamaH,FukuyamaY,HiramaM. 2004.TMC-95A,a reversible proteasome inhibitor, induces neurite outgrowth in PC12 cells. Bioorg. Med. Chem. Lett. 14:663-65
63. Itoh A, Horiuchi M, Bannerman P, Pleasure D, Itoh T. 2009. Impaired regenerative response of primary sensory neurons in ZPK/DLK gene-trap mice. Biochem. Biophys. Res. Commun. 383:258-62
64. Jasper H, Benes V, Schwager C, Sauer S, Clauder-Munster S, et al. 2001. The genomic response of the Drosophila embryo to JNK signaling. Dev. Cell 1:579-86
65. Jayaram HN, Kusumanchi P, Yalowitz JA. 2011. NMNAT expression and its relation to NAD metabolism. Curr. Med. Chem. 18:1962-72
66. Kane RC, Bross PF, Farrell AT, Pazdur R. 2003. Velcade R- : U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. Oncologist. 8:508-13
67. Kaneko-Oshikawa C, Nakagawa T, Yamada M, Yoshikawa H, Matsumoto M, et al. 2005. Mammalian E4 is required for cardiac development and maintenance of the nervous system. Mol. Cell. Biol. 25:10953-64
68. Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, et al. 1987. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325:733-36
69. Keene AC, Waddell S. 2007. Drosophila olfactory memory: single genes to complex neural circuits. Nat. Rev. Neurosci. 8:341-54
70. Kim D, Tsai LH. 2009. Bridging physiology and pathology in AD. Cell 137:997-1000
71. Koushika SP. 2008. JIP ing along the axon: the complex roles of JIPs in axonal transport. Bioessays 30:10-14
72. Korhonen L, Lindholm D. 2004. The ubiquitin proteasome system in synaptic and axonal degeneration: a new twist to an old cycle. J. Cell Biol. 165:27-30
73. Lau C, Niere M, Ziegler M. 2009. The NMN/NaMN adenylyltransferase (NMNAT) protein family. Front. Biosci. 14:410-31
74. Lanier LM, Gertler FB. 2000. From Abl to actin: Abl tyrosine kinase and associated proteins in growth cone motility. Curr. Opin. Neurobiol. 10:80-87
75. Laser H, Mack TG, Wagner D, Coleman MP. 2003. Proteasome inhibition arrests neurite outgrowth and causes dying-back degeneration in primary culture. J. Neurosci. Res. 74:906-16
76. Lehman NL. 2009. The ubiquitin proteasome system in neuropathology. Acta Neuropathol. 118:329-47
77. Lessing D, Bonini NM. 2009. Maintaining the brain: insight into human neurodegeneration from Drosophila melanogaster mutants. Nat. Rev. Genet. 10:359-70
78. Lewcock JW, Genoud N, Lettieri K, Pfaff SL. 2007. The ubiquitin ligase Phr1 regulates axon outgrowth through modulation of microtubule dynamics. Neuron 56:604-20
79. Leyssen M, Ayaz D, Hebert SS, Reeve S, De Strooper B, Hassan BA. 2005. Amyloid precursor protein promotes postdevelopmental neurite arborization in the Drosophila brain. EMBO J. 24:2944-55
80. Lim K-L, Tan JMM. 2007. Role of the ubiquitin proteasome system in Parkinson's disease. BMC Biochem. 8(Suppl 1):S13
81. Low LK,Cheng HJ. 2006. Axon pruning: an essential step underlying the developmental plasticity of neuronal connections. Philos. Trans. R. Soc. Lond. B Biol. Sci. 29:1531-44
82. Ludwin SK, Bisby MA. 1992. Delayed wallerian degeneration in the central nervous system of Ola mice: an ultrastructural study. J. Neurol. Sci. 109:140-47
83. Lunn ER, Perry VH, Brown MC, Rosen H, Gordon S. 1989. Absence of Wallerian degeneration does not hinder regeneration in peripheral nerve. Eur. J. Neurosci. 1:27-33
84. Luo L, O'Leary DD. 2005. Axon retraction and degeneration in development and disease. Annu. Rev. Neurosci. 28:127-56
85. MacDonald JM, Beach MG, Porpiglia E, Sheehan AE, Watts RJ, Freeman MR. 2006. The Drosophila cell corpse engulfment receptor Draper mediates glial clearance of severed axons. Neuron 50:869-81
86. MacInnisBL, Campenot RB. 2005. Regulation ofWallerian degeneration and nerve growth factor withdrawalinduced pruning of axons of sympathetic neurons by the proteasome and the MEK/Erk pathway. Mol. Cell. Neurosci. 28:430-39
87. Mack TG, Reiner M, Beirowski B, Mi W, Emanuelli M, et al. 2001. Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nat. Neurosci. 4:1199-206
88. Marsh JL, Thompson LM. 2006. Drosophila in the study of neurodegenerative disease. Neuron 52:169-78
89. Martin-Morris LE, WhiteK. 1990. The Drosophila transcript encoded by theβ-amyloid protein precursor-like gene is restricted to the nervous system. Development 110:185-95
90. Massaro CM, Pielage J, Davis GW. 2009. Molecular mechanisms that enhance synapse stability despite persistent disruption of the spectrin/ankyrin/ microtubule cytoskeleton. J. Cell Biol. 187:101-17
91. Matsuda S, Yasukawa T, Homma Y, Ito Y, Niikura T, et al. 2001. c-jun N-terminal kinase ( JNK)-interacting protein-1b/islet-brain-1 scaffolds Alzheimer's amyloid precursor protein with JNK. J. Neurosci. 21:6597-607
92. Meyer zuHorsteG,Miesbach TA,Muller JI, Fledrich R, Stassart RM, et al. 2011. TheWlds transgene reduces axon loss in a Charcot-Marie-Tooth disease 1A rat model and nicotinamide delays post-traumatic axonal degeneration. Neurobiol. Dis. 42:1-8
93. Miller BR, Press C, Daniels RW, Sasaki Y,Milbrandt J, DiAntonio A. 2009. A dual leucine kinase-dependent axon self-destruction program promotes Wallerian degeneration. Nat. Neurosci. 12:387-89
94. Mladinic M, Muller KJ, Nicholls JG. 2009. Central nervous system regeneration: from leech to opossum. J. Physiol. 587:2775-82
95. Murakami N, Yamaki T, Iwamoto Y, Sakakibara T, Kobori N, et al. 1998. Experimental brain injury induces expression of amyloid precursor protein, which may be related to neuronal loss in the hippocampus. J. Neurotrauma 15:993-1003
96. Nikiforov A, Dolle C, Niere M, Ziegler M. 2011. Pathways and subcellular compartmentation of NAD biosynthesis in human cells: from entry of extracellular precursors to mitochondrial NAD generation. J. Biol. Chem. 286:21767-78
97. Nikolaev A,McLaughlin T, O'Leary DD, Tessier-Lavigne M. 2009. APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457:981-89
98. Nitabach MN,Taghert PH. 2008. Organization of the Drosophila circadian control circuit. Curr. Biol. 18:R84-93
99. Nix P, Hisamoto N, Matsumoto K, Bastiani M. 2011. Axon regeneration requires coordinate activation of p38 and JNK MAPK pathways. Proc. Natl. Acad. Sci. USA 108:10738-43
100. Panegyres PK. 2001. The functions of the amyloid precursor protein gene. Rev. Neurosci. 12:1-39
101. Park JH, Strittmatter SM. 2007. Nogo receptor interacts with brain APP and Aβto reduce pathologic changes in Alzheimer's transgenic mice. Curr. Alzheimer Res. 4:568-70
102. Perlson E, Maday S, Fu MM, Moughamian AJ, Holzbaur EL. 2010. Retrograde axonal transport: pathways to cell death? Trends Neurosci. 33:335-44
103. Potter CJ, Turenchalk GS, Xu T. 2000. Drosophila in cancer research: an expanding role. Trends Genet. 16:33-39
104. Press C, Milbrandt J. 2008. Nmnat delays axonal degeneration caused by mitochondrial and oxidative stress. J. Neurosci. 28:4861-71
105. Qiu J, Cai D, Dai H, McAtee M, Hoffman PN, et al. 2002. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 34:895-903
106. Rodan AR, Rothenfluh A. 2010. The genetics of behavioral alcohol responses in Drosophila. Int. Rev. Neurobiol. 91:25-51
107. Sasaki Y, Araki T,Milbrandt J. 2006. Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy. J. Neurosci. 26:8484-91
108. Sasaki Y, Milbrandt J. 2010. Axonal degeneration is blocked by nicotinamide mononucleotide adenylyltransferase (Nmnat) protein transduction into transected axons. J. Biol. Chem. 285:41211-15
109. Sasaki Y, Vohra BP, Baloh RH, Milbrandt J. 2009a. Transgenic mice expressing theNmnat1 protein manifest robust delay in axonal degeneration in vivo. J. Neurosci. 29:6526-34
110. Sasaki Y, Vohra BP, Lund FE, Milbrandt J. 2009b. Nicotinamide mononucleotide adenylyl transferasemediated axonal protection requires enzymatic activity but not increased levels of neuronal nicotinamide adenine dinucleotide. J. Neurosci. 29:5525-35
111. Saxena S, Caroni P. 2007. Mechanisms of axon degeneration: from development to disease. Prog. Neurobiol. 83:174-91
112. Schoenmann Z, Assa-Kunik E, Tiomny S, Minis A, Haklai-Topper L, et al. 2010. Axonal degeneration is regulated by the apoptotic machinery or a NAD+-sensitive pathway in insects and mammals. J. Neurosci. 30:6375-86
113. Sehgal A, Joiner W, Crocker A, Koh K, Sathyanarayanan S, et al. 2007. Molecular analysis of sleep: wake cycles in Drosophila. Cold Spring Harb. Symp. Quant. Biol. 72:557-64
114. Shulman JM, Shulman LM,WeinerWJ, Feany MB. 2003. From fruit fly to bedside: translating lessons from Drosophila models of neurodegenerative disease. Curr. Opin. Neurol. 16:443-49
115. Staal JA, Dickson TC, Chung RS, Vickers JC. 2009. Disruption of the ubiquitin proteasome system following axonal stretch injury accelerates progression to secondary axotomy. J. Neurotrauma 26:781-88
116. Simonin Y, Ferrer-Alcon M, Ferri A, Kato AC. 2007. The neuroprotective effects of the WldS gene are correlated with proteasome expression rather than apoptosis. Eur. J. Neurosci. 25:2269-74
117. Song EJ, Hong H-M, Yoo YS. 2009. Proteasome inhibition induces neurite outgrowth through posttranslational modification of TrkA receptor. Int. J. Biochem. Cell Biol. 41:539-45
118. Sorci L, Cimadamore F, Scotti S, Petrelli R, Cappellacci L, et al. 2007. Initial-rate kinetics of human NMNadenylyltransferases: substrate and metal ion specificity, inhibition by products and multisubstrate analogues, and isozyme contributions to NAD+ biosynthesis. Biochemistry 46:4912-22
119. Srahna M, Leyssen M, Choi CM, Fradkin LG, Noordermeer JN, Hassan BA. 2006. A signaling network for patterning of neuronal connectivity in the Drosophila brain. PLoS Biol. 4:e348
120. StoneMC, NguyenMM,Tao J, Allender DL,RollsMM.2010. Global up-regulation ofmicrotubule dynamics and polarity reversal during regeneration of an axon from a dendrite. Mol. Biol. Cell 21:767-77
121. Stone MC, Roegiers F, Rolls MM. 2008. Microtubules have opposite orientation in axons and dendrites of Drosophila neurons. Mol. Biol. Cell 19:4122-29
122. Stowers RS, Megeath LJ, Gorska-Andrzejak J, Meinertzhagen IA, Schwarz TL. 2002. Axonal transport of mitochondria to synapses depends on Milton, a novel Drosophila protein. Neuron 36:1063-77
123. Tao J, Rolls MM. 2011. Dendrites have a rapid program of injury-induced degeneration that is molecularly distinct from developmental pruning. J. Neurosci. 31:5398-405
124. Taru H, Iijima K, Hase M, Kirino Y, Yagi Y, Suzuki T. 2002. Interaction ofAlzheimer's beta-amyloid precursor family proteins with scaffold proteins of the JNK signaling cascade. J. Biol. Chem. 277:20070-78
125. Upadhya SC, Hegde AN. 2007. Role of the ubiquitin proteasome system in Alzheimer's disease. BMC Biochem. 8(Suppl 1):S12
126. Tuszynski MH, Steward O. 2012. Concepts and methods for the study of axonal regeneration in the CNS. Neuron 74:777-91
127. Van Den Heuvel C, Blumbergs PC, Finnie JW, Manavis J, Jones NR, et al. 1999. Upregulation of amyloid precursor protein messenger RNA in response to traumatic brain injury: an ovine head impact model. Exp. Neurol. 159:441-50
128. Vargas ME, Barres BA. 2007. Why is Wallerian degeneration in the CNS so slow? Annu. Rev. Neurosci. 30:153-79
129. Verhey KJ, Rapoport TA. 2001. Kinesin carries the signal. Trends Biochem. Sci. 26:545-50
130. Vidal L, Morin LP. 2007. Absence of normal photic integration in the circadian visual system: response to millisecond light flashes. J. Neurosci. 27:3375-82
131. Vohra BP, Sasaki Y, Miller BR, Chang J,DiAntonio A, Milbrandt J. 2010. Amyloid precursor protein cleavagedependent and -independent axonal degeneration programs share a common nicotinamide mononucleotide adenylyltransferase 1-sensitive pathway. J. Neurosci. 30:13729-38
132. Wan HI, DiAntonio A, Fetter RD, Bergstrom K, Strauss R, Goodman CS. 2000. Highwire regulates synaptic growth in Drosophila. Neuron 26:313-29
133. Wang J, Zhai Q, Chen Y, Lin E, GuW, et al. 2005. A local mechanism mediates NAD-dependent protection of axon degeneration. J. Cell Biol. 170:349-55
134. Wang MS, Davis AA, Culver DG, Glass JD. 2002. WldS mice are resistant to paclitaxel (taxol) neuropathy. Ann. Neurol. 52:442-47
135. Wang MS, Fang G, Culver DG, Davis AA, Rich MM, Glass JD. 2001. The WldS protein protects against axonal degeneration: a model of gene therapy for peripheral neuropathy. Ann. Neurol. 50:773-79
136. Wang MS,Wu Y, Culver DG, Glass JD. 2000. Pathogenesis of axonal degeneration: parallels between Wallerian degeneration and vincristine neuropathy. J. Neuropathol. Exp. Neurol. 59:599-606
137. Wang X, Schwarz TL. 2009. The mechanism of Ca2+-dependent regulation of kinesin-mediated mitochondrial motility. Cell 136:163-74
138. Wang Z, Jin Y. 2011. Genetic dissection of axon regeneration. Curr. Opin. Neurobiol. 21:189-96
139. Watts RJ, Hoopfer ED, Luo L. 2003. Axon pruning during Drosophila metamorphosis: evidence for local degeneration and requirement of the ubiquitin-proteasome system. Neuron 38:871-85
140. Wen Y, Parrish JZ, He R, Zhai RG, Kim MD. 2011. Nmnat exerts neuroprotective effects in dendrites and axons. Mol. Cell. Neurosci. 48:1-8
141. Xiong X, Collins CA. 2012. A conditioning lesion protects axons from degeneration via the Wallenda/DLK MAP kinase signaling cascade. J. Neurosci. 32:610-15
142. Xiong X,Wang X, Ewanek R, Bhat P,Diantonio A,Collins CA. 2010. Protein turnover of theWallenda/DLK kinase regulates a retrograde response to axonal injury. J. Cell Biol. 191:211-23
143. Witte H, Bradke F. 2008. The role of the cytoskeleton during neuronal polarization. Curr. Opin. Neurobiol. 18:479-87
144. Yahata N, Yuasa S, Araki T. 2009. Nicotinamide mononucleotide adenylyltransferase expression in mitochondrial matrix delaysWallerian degeneration. J. Neurosci. 29:6276-84
145. Yan D,Wu Z, Chisholm AD, Jin Y. 2009. The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration. Cell 138:1005-18
146. Yan T, Feng Y, Zheng J, Ge X, Zhang Y, et al. 2010. Nmnat2 delays axon degeneration in superior cervical ganglia dependent on its NAD synthesis activity. Neurochem. Int. 56:101-6
147. Yiu G, He Z. 2006. Glial inhibition of CNS axon regeneration. Nat. Rev. Neurosci. 7:617-27
148. Zandy NL, Pendergast AM. 2008. Abl tyrosine kinases modulate cadherin-dependent adhesion upstream and downstream of Rho family GTPases. Cell Cycle 7:444-48
149. Zhai Q, Wang J, Kim A, Liu Q, Watts R, et al. 2003. Involvement of the ubiquitin-proteasome system in the early stages ofWallerian degeneration. Neuron 39:217-25
150. Zhai RG,Cao Y, Hiesinger PR, Zhou Y, Mehta SQ, et al. 2006. DrosophilaNMNATmaintains neural integrity independent of its NAD synthesis activity. PLoS Biol. 4:e416
151. Zhai RG, Zhang F, Hiesinger PR, Cao Y, Haueter CM, Bellen HJ. 2008. NAD synthase NMNAT acts as a chaperone to protect against neurodegeneration. Nature 452:887-91
152. Zhang S, Zhang Q, Zhang JH, Qin X. 2008. NgR acts as an inhibitor to axonal regeneration in adults. Front. Biosci. 13:2030-40
153. Zhou Z, Hartwieg E, Horvitz HR. 2001. CED-1 is a transmembrane receptor that mediates cell corpse engulfment in C. elegans. Cell 104:43-56
154. Zhou ZD, Chan CH, Ma QH, Xu XH, Xiao ZC, Tan EK. 2011. The roles of amyloid precursor protein (APP) in neurogenesis: implications to pathogenesis and therapy of Alzheimer disease. Cell Adhes. Migr. 5:280-92
155. Ziegenfuss JS, Biswas R, Avery MA, Hong K, Sheehan AE, et al. 2008. Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling. Nature 453:935-39