1932

Abstract

From injury to disease to aging, neurons, like all cells, may face various insults that can impact their function and survival. Although the consequences are substantially dictated by the type, context, and severity of insult, distressed neurons are far from passive. Activation of cellular stress responses aids in the preservation or restoration of nervous system function. However, stress responses themselves can further advance neuropathology and contribute significantly to neuronal dysfunction and neurodegeneration. Here we explore the recent advances in defining the cellular stress responses within neurodegenerative diseases and neuronal injury, and we emphasize axonal injury as a well-characterized model of neuronal insult. We highlight key findings and unanswered questions about neuronal stress response pathways, from the initial detection of cellular insults through the underlying mechanisms of the responses to their ultimate impact on the fates of distressed neurons.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pathol-012414-040354
2018-01-24
2024-06-13
Loading full text...

Full text loading...

/deliver/fulltext/pathol/13/1/annurev-pathol-012414-040354.html?itemId=/content/journals/10.1146/annurev-pathol-012414-040354&mimeType=html&fmt=ahah

Literature Cited

  1. Segev Y, Barrera I, Ounallah-Saad H, Wibrand K, Sporild I. 1.  et al. 2015. PKR inhibition rescues memory deficit and ATF4 overexpression in ApoE ε4 human replacement mice. J. Neurosci. 35:3812986–93 [Google Scholar]
  2. Ma T, Trinh MA, Wexler AJ, Bourbon C, Gatti E. 2.  et al. 2013. Suppression of eIF2α kinases alleviates Alzheimer's disease–related plasticity and memory deficits. Nat. Neurosci. 16:91299–305 [Google Scholar]
  3. Wang L, Popko B, Roos RP. 3.  2014. An enhanced integrated stress response ameliorates mutant SOD1-induced ALS. Hum. Mol. Genet. 23:102629–38 [Google Scholar]
  4. Vieira FG, Ping Q, Moreno AJ, Kidd JD, Thompson K. 4.  et al. 2015. Guanabenz treatment accelerates disease in a mutant SOD1 mouse model of ALS. PLOS ONE 10:8e0135570 [Google Scholar]
  5. Valenzuela V, Collyer E, Armentano D, Parsons GB, Court FA. 5.  et al. 2012. Activation of the unfolded protein response enhances motor recovery after spinal cord injury. Cell Death Dis 3:e272 [Google Scholar]
  6. Ohri SS, Hetman M, Whittemore SR. 6.  2013. Restoring endoplasmic reticulum homeostasis improves functional recovery after spinal cord injury. Neurobiol. Dis. 58:29–37 [Google Scholar]
  7. Hammarlund M, Nix P, Hauth L, Jorgensen EM, Bastiani M. 7.  2009. Axon regeneration requires a conserved MAP kinase pathway. Science 323:5915802–6 [Google Scholar]
  8. Shin JE, Cho Y, Beirowski B, Milbrandt J, Cavalli V, DiAntonio A. 8.  2012. Dual leucine zipper kinase is required for retrograde injury signaling and axonal regeneration. Neuron 74:61015–22 [Google Scholar]
  9. Yan D, Wu Z, Chisholm AD, Jin Y. 9.  2009. The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration. Cell 138:51005–18 [Google Scholar]
  10. Watkins TA, Wang B, Huntwork-Rodriguez S, Yang J, Jiang Z. 10.  et al. 2013. DLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury. PNAS 110:104039–44 [Google Scholar]
  11. Le Pichon C, Meilandt W, Dominguez S, Solanoy H, Lin H. 11.  et al. 2017. Loss of dual leucine zipper kinase signaling is protective in multiple neurodegenerative disease models. Sci. Transl. Med. 9:403eaag0394 [Google Scholar]
  12. Guo X, Disatnik MH, Monbureau M, Shamloo M, Mochly-Rosen D, Qi X. 12.  2013. Inhibition of mitochondrial fragmentation diminishes Huntington's disease–associated neurodegeneration. J. Clin. Investig. 123:125371–88 [Google Scholar]
  13. Poehler AM, Xiang W, Spitzer P, May VE, Meixner H. 13.  et al. 2014. Autophagy modulates SNCA/α-synuclein release, thereby generating a hostile microenvironment. Autophagy 10:122171–92 [Google Scholar]
  14. DeGracia DJ, Rudolph J, Roberts GG, Rafols JA, Wang J. 14.  2007. Convergence of stress granules and protein aggregates in hippocampal cornu ammonis 1 at later reperfusion following global brain ischemia. Neuroscience 146:2562–72 [Google Scholar]
  15. Taylor RC, Berendzen KM, Dillin A. 15.  2014. Systemic stress signalling: understanding the cell non-autonomous control of proteostasis. Nat. Rev. Mol. Cell Biol. 15:3211–17 [Google Scholar]
  16. Koss DJ, Platt B. 16.  2017. Alzheimer's disease pathology and the unfolded protein response: prospective pathways and therapeutic targets. Behav. Pharmacol. 28:2–3161–78 [Google Scholar]
  17. Sweeney P, Park H, Baumann M, Dunlop J, Frydman J. 17.  et al. 2017. Protein misfolding in neurodegenerative diseases: implications and strategies. Transl. Neurodegener. 6:6 [Google Scholar]
  18. Xiang C, Wang Y, Zhang H, Han F. 18.  2017. The role of endoplasmic reticulum stress in neurodegenerative disease. Apoptosis 22:11–26 [Google Scholar]
  19. Shah SZ, Zhao D, Khan SH, Yang L. 19.  2015. Unfolded protein response pathways in neurodegenerative diseases. J. Mol. Neurosci. 57:4529–37 [Google Scholar]
  20. Mattson MP. 20.  2010. ER calcium and Alzheimer's disease: in a state of flux. Sci. Signal 3:114pe10 [Google Scholar]
  21. Popugaeva E, Bezprozvanny I. 21.  2013. Role of endoplasmic reticulum Ca2+ signaling in the pathogenesis of Alzheimer disease. Front. Mol. Neurosci. 6:29 [Google Scholar]
  22. Tu H, Nelson O, Bezprozvanny A, Wang Z, Lee SF. 22.  et al. 2006. Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease–linked mutations. Cell 126:5981–93 [Google Scholar]
  23. Larhammar M, Huntwork-Rodriguez S, Jiang Z, Solanoy H, Sengupta Ghosh A. 23.  et al. 2017. Dual leucine zipper kinase–dependent PERK activation contributes to neuronal degeneration following insult. eLife 6:e20725 [Google Scholar]
  24. Huang YA, Zhou B, Wernig M, Sudhof TC. 24.  2017. ApoE2, ApoE3, and ApoE4 differentially stimulate APP transcription and Aβ secretion. Cell 168:3427–41.e21 [Google Scholar]
  25. Leah JD, Herdegen T, Bravo R. 25.  1991. Selective expression of Jun proteins following axotomy and axonal transport block in peripheral nerves in the rat: evidence for a role in the regeneration process. Brain Res 566:1–2198–207 [Google Scholar]
  26. Valakh V, Walker LJ, Skeath JB, DiAntonio A. 26.  2013. Loss of the spectraplakin short stop activates the DLK injury response pathway in Drosophila. . J. Neurosci. 33:4517863–73 [Google Scholar]
  27. Valakh V, Frey E, Babetto E, Walker LJ, DiAntonio A. 27.  2015. Cytoskeletal disruption activates the DLK/JNK pathway, which promotes axonal regeneration and mimics a preconditioning injury. Neurobiol. Dis. 77:13–25 [Google Scholar]
  28. Hollis ER 2nd, Ishiko N, Tolentino K, Doherty E, Rodriguez MJ. 28.  et al. 2015. A novel and robust conditioning lesion induced by ethidium bromide. Exp. Neurol. 265:30–39 [Google Scholar]
  29. Kirkpatrick LL, Witt AS, Payne HR, Shine HD, Brady ST. 29.  2001. Changes in microtubule stability and density in myelin-deficient shiverer mouse CNS axons. J. Neurosci. 21:72288–97 [Google Scholar]
  30. Ying Z, Zhai R, McLean NA, Johnston JM, Misra V, Verge VM. 30.  2015. The unfolded protein response and cholesterol biosynthesis link Luman/CREB3 to regenerative axon growth in sensory neurons. J. Neurosci. 35:4314557–70 [Google Scholar]
  31. Ghosh-Roy A, Wu Z, Goncharov A, Jin Y, Chisholm AD. 31.  2010. Calcium and cyclic AMP promote axonal regeneration in Caenorhabditis elegans and require DLK-1 kinase. J. Neurosci. 30:93175–83 [Google Scholar]
  32. Yan D, Jin Y. 32.  2012. Regulation of DLK-1 kinase activity by calcium-mediated dissociation from an inhibitory isoform. Neuron 76:3534–48 [Google Scholar]
  33. Xiong X, Wang X, Ewanek R, Bhat P, DiAntonio A, Collins CA. 33.  2010. Protein turnover of the Wallenda/DLK kinase regulates a retrograde response to axonal injury. J. Cell Biol. 191:1211–23 [Google Scholar]
  34. Huntwork-Rodriguez S, Wang B, Watkins T, Ghosh AS, Pozniak CD. 34.  et al. 2013. JNK-mediated phosphorylation of DLK suppresses its ubiquitination to promote neuronal apoptosis. J. Cell Biol. 202:5747–63 [Google Scholar]
  35. Gerdts J, Summers DW, Milbrandt J, DiAntonio A. 35.  2016. Axon self-destruction: new links among SARM1, MAPKs, and NAD+ metabolism. Neuron 89:3449–60 [Google Scholar]
  36. Yang J, Wu Z, Renier N, Simon DJ, Uryu K. 36.  et al. 2015. Pathological axonal death through a MAPK cascade that triggers a local energy deficit. Cell 160:1–2161–76 [Google Scholar]
  37. Walker LJ, Summers DW, Sasaki Y, Brace EJ, Milbrandt J, DiAntonio A. 37.  2017. MAPK signaling promotes axonal degeneration by speeding the turnover of the axonal maintenance factor NMNAT2. eLife 6:e22540 [Google Scholar]
  38. Neumann S, Bradke F, Tessier-Lavigne M, Basbaum AI. 38.  2002. Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron 34:6885–93 [Google Scholar]
  39. Qiu J, Cai D, Dai H, McAtee M, Hoffman PN. 39.  et al. 2002. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 34:6895–903 [Google Scholar]
  40. Hao Y, Frey E, Yoon C, Wong H, Nestorovski D. 40.  et al. 2016. An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK. eLife 5:e14048 [Google Scholar]
  41. Ghosh AS, Wang B, Pozniak CD, Chen M, Watts RJ, Lewcock JW. 41.  2011. DLK induces developmental neuronal degeneration via selective regulation of proapoptotic JNK activity. J. Cell Biol. 194:5751–64 [Google Scholar]
  42. Bazenet CE, Mota MA, Rubin LL. 42.  1998. The small GTP-binding protein Cdc42 is required for nerve growth factor withdrawal-induced neuronal death. PNAS 95:73984–89 [Google Scholar]
  43. Stankiewicz TR, Linseman DA. 43.  2014. Rho family GTPases: key players in neuronal development, neuronal survival, and neurodegeneration. Front. Cell. Neurosci. 8:314 [Google Scholar]
  44. Fujita Y, Yamashita T. 44.  2014. Axon growth inhibition by RhoA/ROCK in the central nervous system. Front. Neurosci. 8:338 [Google Scholar]
  45. Hu Y. 45.  2016. Axon injury induced endoplasmic reticulum stress and neurodegeneration. Neural Regen. Res. 11:101557–59 [Google Scholar]
  46. Jamison JT, Kayali F, Rudolph J, Marshall M, Kimball SR, DeGracia DJ. 46.  2008. Persistent redistribution of poly-adenylated mRNAs correlates with translation arrest and cell death following global brain ischemia and reperfusion. Neuroscience 154:2504–20 [Google Scholar]
  47. Ohno M. 47.  2014. Roles of eIF2α kinases in the pathogenesis of Alzheimer's disease. Front. Mol. Neurosci. 7:22 [Google Scholar]
  48. Bellato HM, Hajj GN. 48.  2016. Translational control by eIF2α in neurons: beyond the stress response. Cytoskeleton 73:10551–65 [Google Scholar]
  49. Pakos-Zebrucka K, Koryga I, Mnich K, Ljujic M, Samali A, Gorman AM. 49.  2016. The integrated stress response. EMBO Rep 17:101374–95 [Google Scholar]
  50. B'Chir W, Maurin AC, Carraro V, Averous J, Jousse C. 50.  et al. 2013. The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic Acids Res 41:167683–99 [Google Scholar]
  51. Garcia-Huerta P, Troncoso-Escudero P, Jerez C, Hetz C, Vidal RL. 51.  2016. The intersection between growth factors, autophagy and ER stress: a new target to treat neurodegenerative diseases?. Brain Res 1649:Pt B173–80 [Google Scholar]
  52. Kouroku Y, Fujita E, Tanida I, Ueno T, Isoai A. 52.  et al. 2007. ER stress (PERK/eIF2α phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Cell Death Differ 14:2230–39 [Google Scholar]
  53. Liu J, Pasini S, Shelanski ML, Greene LA. 53.  2014. Activating transcription factor 4 (ATF4) modulates post-synaptic development and dendritic spine morphology. Front. Cell. Neurosci. 8:177 [Google Scholar]
  54. Pasini S, Corona C, Liu J, Greene LA, Shelanski ML. 54.  2015. Specific downregulation of hippocampal ATF4 reveals a necessary role in synaptic plasticity and memory. Cell Rep 11:2183–91 [Google Scholar]
  55. Sidrauski C, Acosta-Alvear D, Khoutorsky A, Vedantham P, Hearn BR. 55.  et al. 2013. Pharmacological brake-release of mRNA translation enhances cognitive memory. eLife 2:e00498 [Google Scholar]
  56. Paschen W, Proud CG, Mies G. 56.  2007. Shut-down of translation, a global neuronal stress response: mechanisms and pathological relevance. Curr. Pharm. Des. 13:181887–902 [Google Scholar]
  57. Anderson P, Kedersha N. 57.  2008. Stress granules: the Tao of RNA triage. Trends Biochem. Sci. 33:3141–50 [Google Scholar]
  58. Aulas A, Fay MM, Lyons SM, Achorn CA, Kedersha N. 58.  et al. 2017. Stress-specific differences in assembly and composition of stress granules and related foci. J. Cell Sci. 130:5927–37 [Google Scholar]
  59. McInerney GM, Kedersha NL, Kaufman RJ, Anderson P, Liljestrom P. 59.  2005. Importance of eIF2α phosphorylation and stress granule assembly in alphavirus translation regulation. Mol. Biol. Cell 16:83753–63 [Google Scholar]
  60. Bentmann E, Haass C, Dormann D. 60.  2013. Stress granules in neurodegeneration—lessons learnt from TAR DNA binding protein of 43 kDa and fused in sarcoma. FEBS J 280:184348–70 [Google Scholar]
  61. Johnson IP, Sears TA. 61.  2013. Target-dependence of sensory neurons: an ultrastructural comparison of axotomised dorsal root ganglion neurons with allowed or denied reinnervation of peripheral targets. Neuroscience 228:163–78 [Google Scholar]
  62. Moisse K, Volkening K, Leystra-Lantz C, Welch I, Hill T, Strong MJ. 62.  2009. Divergent patterns of cytosolic TDP-43 and neuronal progranulin expression following axotomy: implications for TDP-43 in the physiological response to neuronal injury. Brain Res 1249:202–11 [Google Scholar]
  63. Vanderweyde T, Yu H, Varnum M, Liu-Yesucevitz L, Citro A. 63.  et al. 2012. Contrasting pathology of the stress granule proteins TIA-1 and G3BP in tauopathies. J. Neurosci. 32:248270–83 [Google Scholar]
  64. Fan AC, Leung AK. 64.  2016. RNA granules and diseases: a case study of stress granules in ALS and FTLD. Adv. Exp. Med. Biol. 907:263–96 [Google Scholar]
  65. Kedersha N, Chen S, Gilks N, Li W, Miller IJ. 65.  et al. 2002. Evidence that ternary complex (eIF2-GTP-tRNAiMet)–deficient preinitiation complexes are core constituents of mammalian stress granules. Mol. Biol. Cell 13:1195–210 [Google Scholar]
  66. Kedersha NL, Gupta M, Li W, Miller I, Anderson P. 66.  1999. RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2α to the assembly of mammalian stress granules. J. Cell Biol. 147:71431–42 [Google Scholar]
  67. Ohn T, Kedersha N, Hickman T, Tisdale S, Anderson P. 67.  2008. A functional RNAi screen links O-GlcNAc modification of ribosomal proteins to stress granule and processing body assembly. Nat. Cell Biol. 10:101224–31 [Google Scholar]
  68. Ferraris D, Yang Z, Welsbie D. 68.  2013. Dual leucine zipper kinase as a therapeutic target for neurodegenerative conditions. Future Med. Chem. 5:161923–34 [Google Scholar]
  69. Tedeschi A, Bradke F. 69.  2013. The DLK signalling pathway—a double-edged sword in neural development and regeneration. EMBO Rep 14:7605–14 [Google Scholar]
  70. Pozniak CD, Ghosh AS, Gogineni A, Hanson JE, Lee SH. 70.  et al. 2013. Dual leucine zipper kinase is required for excitotoxicity-induced neuronal degeneration. J. Exp. Med. 210:122553–67 [Google Scholar]
  71. Hirai S, Kawaguchi A, Suenaga J, Ono M, Cui DF, Ohno S. 71.  2005. Expression of MUK/DLK/ZPK, an activator of the JNK pathway, in the nervous systems of the developing mouse embryo. Gene Expr. Patterns 5:4517–23 [Google Scholar]
  72. Welsbie DS, Yang Z, Ge Y, Mitchell KL, Zhou X. 72.  et al. 2013. Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death. PNAS 110:104045–50 [Google Scholar]
  73. Chen X, Rzhetskaya M, Kareva T, Bland R, During MJ. 73.  et al. 2008. Antiapoptotic and trophic effects of dominant-negative forms of dual leucine zipper kinase in dopamine neurons of the substantia nigra in vivo. J. Neurosci. 28:3672–80 [Google Scholar]
  74. Chen M, Geoffroy CG, Wong HN, Tress O, Nguyen MT. 74.  et al. 2016. Leucine zipper-bearing kinase promotes axon growth in mammalian central nervous system neurons. Sci. Rep. 6:31482 [Google Scholar]
  75. Welsbie DS, Mitchell KL, Jaskula-Ranga V, Sluch VM, Yang Z. 75.  et al. 2017. Enhanced functional genomic screening identifies novel mediators of dual leucine zipper kinase–dependent injury signaling in neurons. Neuron 94:61142–54 [Google Scholar]
  76. Rishal I, Fainzilber M. 76.  2014. Axon-soma communication in neuronal injury. Nat. Rev. Neurosci. 15:132–42 [Google Scholar]
  77. Zeke A, Misheva M, Remenyi A, Bogoyevitch MA. 77.  2016. JNK signaling: regulation and functions based on complex protein-protein partnerships. Microbiol. Mol. Biol. Rev. 80:3793–835 [Google Scholar]
  78. Kukekov NV, Xu Z, Greene LA. 78.  2006. Direct interaction of the molecular scaffolds POSH and JIP is required for apoptotic activation of JNKs. J. Biol. Chem. 281:2215517–24 [Google Scholar]
  79. Holland SM, Collura KM, Ketschek A, Noma K, Ferguson TA. 79.  et al. 2016. Palmitoylation controls DLK localization, interactions and activity to ensure effective axonal injury signaling. PNAS 113:3763–68 [Google Scholar]
  80. Wang C, Tao Y, Wang Y, Xu Z. 80.  2010. Regulation of the protein stability of POSH and MLK family. Protein Cell 1:9871–78 [Google Scholar]
  81. Nihalani D, Wong HN, Holzman LB. 81.  2003. Recruitment of JNK to JIP1 and JNK-dependent JIP1 phosphorylation regulates JNK module dynamics and activation. J. Biol. Chem. 278:3128694–702 [Google Scholar]
  82. Abe N, Cavalli V. 82.  2008. Nerve injury signaling. Curr. Opin. Neurobiol. 18:3276–83 [Google Scholar]
  83. Perry RB, Fainzilber M. 83.  2014. Local translation in neuronal processes—in vivo tests of a “heretical hypothesis.”. Dev. Neurobiol. 74:3210–17 [Google Scholar]
  84. Ben-Yaakov K, Dagan SY, Segal-Ruder Y, Shalem O, Vuppalanchi D. 84.  et al. 2012. Axonal transcription factors signal retrogradely in lesioned peripheral nerve. EMBO J 31:61350–63 [Google Scholar]
  85. Cavalli V, Kujala P, Klumperman J, Goldstein LS. 85.  2005. Sunday Driver links axonal transport to damage signaling. J. Cell Biol. 168:5775–87 [Google Scholar]
  86. Holland SM, Thomas GM. 86.  2017. Roles of palmitoylation in axon growth, degeneration and regeneration. J. Neurosci. Res. 95:81528–39 [Google Scholar]
  87. Fernandes KJ, Fan DP, Tsui BJ, Cassar SL, Tetzlaff W. 87.  1999. Influence of the axotomy to cell body distance in rat rubrospinal and spinal motoneurons: differential regulation of GAP-43, tubulins, and neurofilament-M. J. Comp. Neurol. 414:4495–510 [Google Scholar]
  88. Nielson JL, Sears-Kraxberger I, Strong MK, Wong JK, Willenberg R, Steward O. 88.  2010. Unexpected survival of neurons of origin of the pyramidal tract after spinal cord injury. J. Neurosci. 30:3411516–28 [Google Scholar]
  89. You SW, So KF, Yip HK. 89.  2000. Axonal regeneration of retinal ganglion cells depending on the distance of axotomy in adult hamsters. Investig. Ophthalmol. Vis. Sci. 41:103165–70 [Google Scholar]
  90. Villegas-Perez MP, Vidal-Sanz M, Rasminsky M, Bray GM, Aguayo AJ. 90.  1993. Rapid and protracted phases of retinal ganglion cell loss follow axotomy in the optic nerve of adult rats. J. Neurobiol. 24:123–36 [Google Scholar]
  91. Richardson PM, Issa VM. 91.  1984. Peripheral injury enhances central regeneration of primary sensory neurones. Nature 309:5971791–93 [Google Scholar]
  92. Berkelaar M, Clarke DB, Wang YC, Bray GM, Aguayo AJ. 92.  1994. Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats. J. Neurosci. 14:74368–74 [Google Scholar]
  93. Mason MR, Lieberman AR, Anderson PN. 93.  2003. Corticospinal neurons up-regulate a range of growth-associated genes following intracortical, but not spinal, axotomy. Eur. J. Neurosci. 18:4789–802 [Google Scholar]
  94. Baleriola J, Walker CA, Jean YY, Crary JF, Troy CM. 94.  et al. 2014. Axonally synthesized ATF4 transmits a neurodegenerative signal across brain regions. Cell 158:51159–72 [Google Scholar]
  95. Verma P, Chierzi S, Codd AM, Campbell DS, Meyer RL. 95.  et al. 2005. Axonal protein synthesis and degradation are necessary for efficient growth cone regeneration. J. Neurosci. 25:2331–42 [Google Scholar]
  96. Perry RB, Doron-Mandel E, Iavnilovitch E, Rishal I, Dagan SY. 96.  et al. 2012. Subcellular knockout of importin β1 perturbs axonal retrograde signaling. Neuron 75:2294–305 [Google Scholar]
  97. Twiss JL, Kalinski AL, Sachdeva R, Houle JD. 97.  2016. Intra-axonal protein synthesis—a new target for neural repair?. Neural Regen. Res. 11:91365–67 [Google Scholar]
  98. Kalinski AL, Sachdeva R, Gomes C, Lee SJ, Shah Z. 98.  et al. 2015. mRNAs and protein synthetic machinery localize into regenerating spinal cord axons when they are provided a substrate that supports growth. J. Neurosci. 35:2810357–70 [Google Scholar]
  99. Stone MC, Albertson RM, Chen L, Rolls MM. 99.  2014. Dendrite injury triggers DLK-independent regeneration. Cell Rep 6:2247–53 [Google Scholar]
  100. Chung SH, Awal MR, Shay J, McLoed MM, Mazur E, Gabel CV. 100.  2016. Novel DLK-independent neuronal regeneration in Caenorhabditis elegans shares links with activity-dependent ectopic outgrowth. PNAS 113:20E2852–60 [Google Scholar]
  101. Ma TC, Willis DE. 101.  2015. What makes a RAG regeneration associated?. Front. Mol. Neurosci. 8:43 [Google Scholar]
  102. Norsworthy MW, Bei F, Kawaguchi R, Wang Q, Tran NM. 102.  et al. 2017. Sox11 expression promotes regeneration of some retinal ganglion cell types but kills others. Neuron 94:61112–1120 [Google Scholar]
  103. Sevastou I, Pryce G, Baker D, Selwood DL. 103.  2016. Characterisation of transcriptional changes in the spinal cord of the progressive experimental autoimmune encephalomyelitis Biozzi ABH mouse model by RNA sequencing. PLOS ONE 11:6e0157754 [Google Scholar]
  104. Kanaan NM, Collier TJ, Cole-Strauss A, Grabinski T, Mattingly ZR. 104.  et al. 2015. The longitudinal transcriptomic response of the substantia nigra to intrastriatal 6-hydroxydopamine reveals significant upregulation of regeneration-associated genes. PLOS ONE 10:5e0127768 [Google Scholar]
  105. Marklund N, Fulp CT, Shimizu S, Puri R, McMillan A. 105.  et al. 2006. Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat. Exp. Neurol. 197:170–83 [Google Scholar]
  106. Henriques A, Kastner S, Chatzikonstantinou E, Pitzer C, Plaas C. 106.  et al. 2014. Gene expression changes in spinal motoneurons of the SOD1(G93A) transgenic model for ALS after treatment with G-CSF. Front. Cell. Neurosci. 8:464 [Google Scholar]
  107. Taylor RC, Cullen SP, Martin SJ. 107.  2008. Apoptosis: controlled demolition at the cellular level. Nat. Rev. Mol. Cell Biol. 9:3231–41 [Google Scholar]
  108. McKernan DP, Cotter TG. 108.  2007. A critical role for Bim in retinal ganglion cell death. J. Neurochem. 102:3922–30 [Google Scholar]
  109. Biswas SC, Shi Y, Sproul A, Greene LA. 109.  2007. Pro-apoptotic Bim induction in response to nerve growth factor deprivation requires simultaneous activation of three different death signaling pathways. J. Biol. Chem. 282:4029368–74 [Google Scholar]
  110. Aime P, Sun X, Zareen N, Rao A, Berman Z. 110.  et al. 2015. Trib3 is elevated in Parkinson's disease and mediates death in Parkinson's disease models. J. Neurosci. 35:3010731–49 [Google Scholar]
  111. Saleem S, Biswas SC. 111.  2017. Tribbles pseudokinase 3 induces both apoptosis and autophagy in amyloid-β-induced neuronal death. J. Biol. Chem. 292:72571–85 [Google Scholar]
  112. Karuppagounder SS, Alim I, Khim SJ, Bourassa MW, Sleiman SF. 112.  et al. 2016. Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models. Sci. Transl. Med. 8:328328ra29 [Google Scholar]
  113. Maor-Nof M, Romi E, Sar Shalom H, Ulisse V, Raanan C. 113.  et al. 2016. Axonal degeneration is regulated by a transcriptional program that coordinates expression of pro- and anti-degenerative factors. Neuron 92:5991–1006 [Google Scholar]
  114. Buckingham BP, Inman DM, Lambert W, Oglesby E, Calkins DJ. 114.  et al. 2008. Progressive ganglion cell degeneration precedes neuronal loss in a mouse model of glaucoma. J. Neurosci. 28:112735–44 [Google Scholar]
  115. Soto I, Oglesby E, Buckingham BP, Son JL, Roberson ED. 115.  et al. 2008. Retinal ganglion cells downregulate gene expression and lose their axons within the optic nerve head in a mouse glaucoma model. J. Neurosci. 28:2548–61 [Google Scholar]
  116. Pak W, Hindges R, Lim YS, Pfaff SL, O'Leary DD. 116.  2004. Magnitude of binocular vision controlled by islet-2 repression of a genetic program that specifies laterality of retinal axon pathfinding. Cell 119:4567–78 [Google Scholar]
  117. Wu F, Kaczynski TJ, Sethuramanujam S, Li R, Jain V. 117.  et al. 2015. Two transcription factors, Pou4f2 and Isl1, are sufficient to specify the retinal ganglion cell fate. PNAS 112:13E1559–68 [Google Scholar]
  118. Stankowska DL, Minton AZ, Rutledge MA, Mueller BH 2nd, Phatak NR. 118.  et al. 2015. Neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma. Investig. Ophthalmol. Vis. Sci. 56:2893–907 [Google Scholar]
  119. Phatak NR, Stankowska DL, Krishnamoorthy RR. 119.  2016. Bcl-2, Bcl-xL, and p-AKT are involved in neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma. Mol. Vis. 22:1048–61 [Google Scholar]
  120. Srinivasan K, Friedman BA, Larson JL, Lauffer BE, Goldstein LD. 120.  et al. 2016. Untangling the brain's neuroinflammatory and neurodegenerative transcriptional responses. Nat Commun 7:11295 [Google Scholar]
  121. Kwon MJ, Shin HY, Cui Y, Kim H, Thi AH. 121.  et al. 2015. CCL2 mediates neuron-macrophage interactions to drive proregenerative macrophage activation following preconditioning injury. J. Neurosci. 35:4815934–47 [Google Scholar]
  122. Niemi JP, DeFrancesco-Lisowitz A, Roldan-Hernandez L, Lindborg JA, Mandell D, Zigmond RE. 122.  2013. A critical role for macrophages near axotomized neuronal cell bodies in stimulating nerve regeneration. J. Neurosci. 33:4116236–48 [Google Scholar]
  123. Niemi JP, DeFrancesco-Lisowitz A, Cregg JM, Howarth M, Zigmond RE. 123.  2016. Overexpression of the monocyte chemokine CCL2 in dorsal root ganglion neurons causes a conditioning-like increase in neurite outgrowth and does so via a STAT3 dependent mechanism. Exp. Neurol. 275:Pt 125–37 [Google Scholar]
  124. Kirchner S, Ignatova Z. 124.  2015. Emerging roles of tRNA in adaptive translation, signalling dynamics and disease. Nat. Rev. Genet. 16:298–112 [Google Scholar]
  125. Guo M, Schimmel P. 125.  2013. Essential nontranslational functions of tRNA synthetases. Nat. Chem. Biol. 9:3145–53 [Google Scholar]
  126. Casas-Tinto S, Lolo FN, Moreno E. 126.  2015. Active JNK-dependent secretion of Drosophila Tyrosyl-tRNA synthetase by loser cells recruits haemocytes during cell competition. Nat. Commun. 6:10022 [Google Scholar]
  127. Orsini F, De Blasio D, Zangari R, Zanier ER, De Simoni M-G. 127.  2014. Versatility of the complement system in neuroinflammation, neurodegeneration and brain homeostasis. Front. Cell. Neurosci. 8:380 [Google Scholar]
  128. Stephan AH, Barres BA, Stevens B. 128.  2012. The complement system: an unexpected role in synaptic pruning during development and disease. Annu. Rev. Neurosci. 35:369–89 [Google Scholar]
  129. Harrington EA, Fanidi A, Evan GI. 129.  1994. Oncogenes and cell death. Curr. Opin. Genet. Dev. 4:1120–29 [Google Scholar]
  130. Hoffman B, Liebermann DA. 130.  2008. Apoptotic signaling by c-MYC. Oncogene 27:506462–72 [Google Scholar]
  131. Benowitz LI, He Z, Goldberg JL. 131.  2017. Reaching the brain: advances in optic nerve regeneration. Exp. Neurol. 287:3365–73 [Google Scholar]
  132. Hu Y, Park KK, Yang L, Wei X, Yang Q. 132.  et al. 2012. Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells. Neuron 73:3445–52 [Google Scholar]
  133. Rich KM, Disch SP, Eichler ME. 133.  1989. The influence of regeneration and nerve growth factor on the neuronal cell body reaction to injury. J. Neurocytol. 18:5569–76 [Google Scholar]
  134. McKay Hart A, Brannstrom T, Wiberg M, Terenghi G. 134.  2002. Primary sensory neurons and satellite cells after peripheral axotomy in the adult rat: timecourse of cell death and elimination. Exp. Brain Res. 142:3308–18 [Google Scholar]
  135. Perlson E, Jeong GB, Ross JL, Dixit R, Wallace KE. 135.  et al. 2009. A switch in retrograde signaling from survival to stress in rapid-onset neurodegeneration. J. Neurosci. 29:319903–17 [Google Scholar]
  136. Miller FD, Pozniak CD, Walsh GS. 136.  2000. Neuronal life and death: an essential role for the p53 family. Cell Death Differ 7:10880–88 [Google Scholar]
  137. Lanni C, Racchi M, Memo M, Govoni S, Uberti D. 137.  2012. p53 at the crossroads between cancer and neurodegeneration. Free Radic. Biol. Med. 52:91727–33 [Google Scholar]
  138. Herrup K, Yang Y. 138.  2007. Cell cycle regulation in the postmitotic neuron: oxymoron or new biology?. Nat. Rev. Neurosci. 8:5368–78 [Google Scholar]
  139. Frade JM, Ovejero-Benito MC. 139.  2015. Neuronal cell cycle: the neuron itself and its circumstances. Cell Cycle 14:5712–20 [Google Scholar]
  140. Norambuena A, Wallrabe H, McMahon L, Silva A, Swanson E. 140.  et al. 2017. mTOR and neuronal cell cycle reentry: how impaired brain insulin signaling promotes Alzheimer's disease. Alzheimers Dement 13:2152–67 [Google Scholar]
  141. Wang L, Popko B, Tixier E, Roos RP. 141.  2014. Guanabenz, which enhances the unfolded protein response, ameliorates mutant SOD1-induced amyotrophic lateral sclerosis. Neurobiol. Dis. 71:317–24 [Google Scholar]
  142. Calabrese V, Cornelius C, Dinkova-Kostova AT, Calabrese EJ, Mattson MP. 142.  2010. Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid. Redox Signal. 13:111763–811 [Google Scholar]
  143. Mattson MP. 143.  2008. Hormesis and disease resistance: activation of cellular stress response pathways. Hum. Exp. Toxicol. 27:2155–62 [Google Scholar]
  144. DeGracia DJ, Hu BR. 144.  2007. Irreversible translation arrest in the reperfused brain. J. Cereb. Blood Flow Metab. 27:875–93 [Google Scholar]
  145. Majd S, Power JH, Grantham HJ. 145.  2015. Neuronal response in Alzheimer's and Parkinson's disease: the effect of toxic proteins on intracellular pathways. BMC Neurosci 16:69 [Google Scholar]
  146. Itoh K, Nakamura K, Iijima M, Sesaki H. 146.  2013. Mitochondrial dynamics in neurodegeneration. Trends Cell Biol 23:64–71 [Google Scholar]
  147. Asiimwe N, Yeo SG, Kim MS, Jung J, Jeong NY. 147.  2016. Nitric oxide: exploring the contextual link with Alzheimer's disease. Oxid. Med. Cell. Longev. 2016:7205747 [Google Scholar]
  148. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. 148.  2010. Mechanisms underlying inflammation in neurodegeneration. Cell 140:918–34 [Google Scholar]
  149. Patel VP, Chu CT. 149.  2011. Nuclear transport, oxidative stress, and neurodegeneration. Int. J. Clin. Exp. Pathol. 4:215–29 [Google Scholar]
  150. Chen L, Liu B. 150.  2017. Relationships between stress granules, oxidative stress, and neurodegenerative diseases. Oxid. Med. Cell. Longev. 2017:1809592 [Google Scholar]
/content/journals/10.1146/annurev-pathol-012414-040354
Loading
/content/journals/10.1146/annurev-pathol-012414-040354
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error