Advertisement

To Survive or to Die: How Neurons Deal with it

  • Yubin Wang
  • Xiaoning Bi
  • Michel Baudry
Chapter

Abstract

Unlike the majority of cells in the organism, neurons have only two options during their entire existence, to survive or to die. As a result, they have evolved elaborate mechanisms to determine which path they will follow in response to a multitude of internal and external signals, and to the wear-and-tear associated with the aging process. Until recently, activation of the calcium-dependent protease, calpain, had been traditionally associated with neurodegeneration. This chapter will review recent findings that indicate that two of the major calpain isoforms present in the brain, calpain-1 and calpain-2, play opposite functions in neuronal survival/death. Thus, calpain-1 activation, downstream of synaptic NMDA receptors, is part of a neuronal survival pathway through the truncation of PHLPP1 and the stimulation of the Akt pathway. In contrast, calpain-2 activation is downstream of extrasynaptic NMDA receptors and is neurodegenerative through the truncation of the phosphatase, STEP, and the activation of the p38 protein kinase. These findings have major significance for our understanding of neurological conditions associated with neurodegeneration and for the development of new therapeutic approaches to prevent neuronal death in these disorders.

Keywords

Calpain-1 Calpain-2 Neuronal death Neuronal survival NMDA receptors Akt STEP 

Notes

Acknowledgements

This work was supported by grant P01NS045260-01 from NINDS (PI: Dr. C.M. Gall), grant R01NS057128 from NINDS to M.B., and grant R15MH101703 from NIMH to X.B. X.B. is also supported by funds from the Daljit and Elaine Sarkaria Chair.

References

  1. Anagli J, Han Y, Stewart L, Yang D, Movsisyan A, Abounit K, Seyfried D (2009) A novel calpastatin-based inhibitor improves postischemic neurological recovery. Biochem Biophys Res Commun 385(1):94–99CrossRefPubMedGoogle Scholar
  2. Arias E, Koga H, Diaz A, Mocholi E, Patel B, Cuervo AM (2015) Lysosomal mTORC2/PHLPP1/Akt regulate chaperone-mediated autophagy. Mol Cell 59(2):270–284. https://doi.org/10.1016/j.molcel.2015.05.030 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Azuma M, Shearer T (2008) The role of calcium-activated protease calpain in experimental retinal pathology. Surv Ophthalmol 53(2):150–163CrossRefPubMedPubMedCentralGoogle Scholar
  4. Bains M, Cebak JE, Gilmer LK, Barnes CC, Thompson SN, Geddes JW, Hall ED (2013) Pharmacological analysis of the cortical neuronal cytoskeletal protective efficacy of the calpain inhibitor SNJ-1945 in a mouse traumatic brain injury model. J Neurochem 125(1):125–132CrossRefPubMedGoogle Scholar
  5. Balazs R, Jorgensen OS, Hack N (1988) N-methyl-D-aspartate promotes the survival of cerebellar granule cells in culture. Neuroscience 27(2):437–451CrossRefPubMedGoogle Scholar
  6. Bartus RT, Baker KL, Heiser AD, Sawyer SD, Dean RL, Elliott PJ, Straub JA (1994a) Postischemic administration of AK275, a calpain inhibitor, provides substantial protection against focal ischemic brain damage. J Cereb Blood Flow Metab 14(4):537–544. https://doi.org/10.1038/jcbfm.1994.67 CrossRefPubMedGoogle Scholar
  7. Bartus RT, Hayward NJ, Elliott PJ, Sawyer SD, Baker KL, Dean RL, Akiyama A, Straub JA, Harbeson SL, Li Z et al (1994b) Calpain inhibitor AK295 protects neurons from focal brain ischemia. Effects of postocclusion intra-arterial administration. Stroke 25(11):2265–2270CrossRefPubMedGoogle Scholar
  8. Baudry M, Bi X (2016) Calpain-1 and Calpain-2: the Yin and Yang of synaptic plasticity and neurodegeneration. Trends Neurosci 39(4):235–245. https://doi.org/10.1016/j.tins.2016.01.007 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Baudry M, Simonson L, Dubrin R, Lynch G (1986) A comparative study of soluble calcium-dependent proteolytic activity in brain. J Neurobiol 17(1):15–28. https://doi.org/10.1002/neu.480170103 CrossRefPubMedGoogle Scholar
  10. Bevers MB, Lawrence E, Maronski M, Starr N, Amesquita M, Neumar RW (2009) Knockdown of m-calpain increases survival of primary hippocampal neurons following NMDA excitotoxicity. J Neurochem 108(5):1237–1250CrossRefPubMedPubMedCentralGoogle Scholar
  11. Boda B, Mendez P, Boury-Jamot B, Magara F, Muller D (2014) Reversal of activity-mediated spine dynamics and learning impairment in a mouse model of Fragile X syndrome. Eur J Neurosci 39(7):1130–1137. https://doi.org/10.1111/ejn.12488 CrossRefPubMedGoogle Scholar
  12. Briz V, Hsu Y-T, Li Y, Lee E, Bi X, Baudry M (2013) Calpain-2-mediated PTEN degradation contributes to BDNF-induced stimulation of dendritic protein synthesis. J Neurosci 33(10):4317–4328CrossRefPubMedPubMedCentralGoogle Scholar
  13. Cagmat EB, Guingab-Cagmat JD, Vakulenko AV, Hayes RL, Anagli J (2015) Potential use of calpain inhibitors as brain injury therapy. In: Kobeissy FH (ed) Brain neurotrauma: molecular, neuropsychological, and rehabilitation aspects. CRC Press/Taylor & Francis, Boca Raton, FL. Chapter 40. Frontiers in NeuroengineeringGoogle Scholar
  14. Chazot PL (2004) The NMDA receptor NR2B subunit: a valid therapeutic target for multiple CNS pathologies. Curr Med Chem 11(3):389–396CrossRefPubMedGoogle Scholar
  15. Chen M, Pratt CP, Zeeman ME, Schultz N, Taylor BS, O'Neill A, Castillo-Martin M, Nowak DG, Naguib A, Grace DM, Murn J, Navin N, Atwal GS, Sander C, Gerald WL, Cordon-Cardo C, Newton AC, Carver BS, Trotman LC (2011) Identification of PHLPP1 as a tumor suppressor reveals the role of feedback activation in PTEN-mutant prostate cancer progression. Cancer Cell 20(2):173–186. https://doi.org/10.1016/j.ccr.2011.07.013 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Chen B, Van Winkle JA, Lyden PD, Brown JH, Purcell NH (2013) PHLPP1 gene deletion protects the brain from ischemic injury. J Cereb Blood Flow Metab 33(2):196–204CrossRefPubMedGoogle Scholar
  17. Chiu K, Lam TT, Ying Li WW, Caprioli J, Kwong Kwong JM (2005) Calpain and N-methyl-d-aspartate (NMDA)-induced excitotoxicity in rat retinas. Brain Res 1046(1–2):207–215. https://doi.org/10.1016/j.brainres.2005.04.016 CrossRefPubMedGoogle Scholar
  18. Donkor IO (2011) Calpain inhibitors: a survey of compounds reported in the patent and scientific literature. Expert Opin Ther Pat 21(5):601–636CrossRefPubMedGoogle Scholar
  19. Downward J (1999) How BAD phosphorylation is good for survival. Nat Cell Biol 1(2):E33–E35CrossRefPubMedGoogle Scholar
  20. Du K, Montminy M (1998) CREB is a regulatory target for the protein kinase Akt/PKB. J Biol Chem 273(49):32377–32379CrossRefPubMedGoogle Scholar
  21. Forman OP, De Risio L, Mellersh CS (2013) Missense mutation in CAPN1 is associated with spinocerebellar ataxia in the Parson Russell Terrier dog breed. PLoS One 8(5):e64627. https://doi.org/10.1371/journal.pone.0064627 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Frey U, Morris RG (1998) Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation. Trends Neurosci 21(5):181–188CrossRefPubMedGoogle Scholar
  23. Gan-Or Z, Bouslam N, Birouk N, Lissouba A, Chambers DB, Veriepe J, Androschuck A, Laurent SB, Rochefort D, Spiegelman D, Dionne-Laporte A, Szuto A, Liao M, Figlewicz DA, Bouhouche A, Benomar A, Yahyaoui M, Ouazzani R, Yoon G, Dupre N, Suchowersky O, Bolduc FV, Parker JA, Dion PA, Drapeau P, Rouleau GA, Bencheikh BO (2016) Mutations in CAPN1 cause autosomal-recessive hereditary spastic paraplegia. Am J Hum Genet 98(5):1038–1046. https://doi.org/10.1016/j.ajhg.2016.04.002 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Gao T, Furnari F, Newton AC (2005) PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth. Mol Cell 18(1):13–24CrossRefPubMedGoogle Scholar
  25. Hamakubo T, Kannagi R, Murachi T, Matus A (1986) Distribution of calpains I and II in rat brain. J Neurosci 6(11):3103–3111CrossRefPubMedGoogle Scholar
  26. Hardingham GE, Bading H (2010) Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat Rev Neurosci 11(10):682–696CrossRefPubMedPubMedCentralGoogle Scholar
  27. Hardingham GE, Arnold FJ, Bading H (2001) Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity. Nat Neurosci 4(3):261–267CrossRefPubMedGoogle Scholar
  28. Hashimoto K, Fukaya M, Qiao X, Sakimura K, Watanabe M, Kano M (1999) Impairment of AMPA receptor function in cerebellar granule cells of ataxic mutant mouse stargazer. J Neurosci 19(14):6027–6036CrossRefPubMedGoogle Scholar
  29. Hong SC, Goto Y, Lanzino G, Soleau S, Kassell NF, Lee KS (1994) Neuroprotection with a calpain inhibitor in a model of focal cerebral ischemia. Stroke 25(3):663–669CrossRefPubMedGoogle Scholar
  30. Jackson TC, Verrier JD, Semple-Rowland S, Kumar A, Foster TC (2010) PHLPP1 splice variants differentially regulate AKT and PKCα signaling in hippocampal neurons: characterization of PHLPP proteins in the adult hippocampus. J Neurochem 115(4):941–955CrossRefPubMedPubMedCentralGoogle Scholar
  31. Kim AH, Khursigara G, Sun X, Franke TF, Chao MV (2001) Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1. Mol Cell Biol 21(3):893–901CrossRefPubMedPubMedCentralGoogle Scholar
  32. Kim JC, Cook MN, Carey MR, Shen C, Regehr WG, Dymecki SM (2009) Linking genetically defined neurons to behavior through a broadly applicable silencing allele. Neuron 63(3):305–315. https://doi.org/10.1016/j.neuron.2009.07.010 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Kobeissy FH, Liu MC, Yang Z, Zhang Z, Zheng W, Glushakova O, Mondello S, Anagli J, Hayes RL, Wang KK (2015) Degradation of βII-Spectrin protein by Calpain-2 and Caspase-3 under neurotoxic and traumatic brain injury conditions. Mol Neurobiol 52(1):696–709CrossRefPubMedGoogle Scholar
  34. Koumura A, Nonaka Y, Hyakkoku K, Oka T, Shimazawa M, Hozumi I, Inuzuka T, Hara H (2008) A novel calpain inhibitor,((1S)-1 ((((1S)-1-benzyl-3-cyclopropylamino-2, 3-di-oxopropyl) amino) carbonyl)-3-methylbutyl) carbamic acid 5-methoxy-3-oxapentyl ester, protects neuronal cells from cerebral ischemia-induced damage in mice. Neuroscience 157(2):309–318CrossRefPubMedGoogle Scholar
  35. Krapivinsky G, Krapivinsky L, Manasian Y, Ivanov A, Tyzio R, Pellegrino C, Ben-Ari Y, Clapham DE, Medina I (2003) The NMDA receptor is coupled to the ERK pathway by a direct interaction between NR2B and RasGRF1. Neuron 40(4):775–784CrossRefPubMedGoogle Scholar
  36. Li PA, Howlett W, He QP, Miyashita H, Siddiqui M, Shuaib A (1998) Postischemic treatment with calpain inhibitor MDL 28170 ameliorates brain damage in a gerbil model of global ischemia. Neurosci Lett 247(1):17–20CrossRefPubMedGoogle Scholar
  37. Li D, Qu Y, Mao M, Zhang X, Li J, Ferriero D, Mu D (2009) Involvement of the PTEN-AKT-FOXO3a pathway in neuronal apoptosis in developing rat brain after hypoxia-ischemia. J Cereb Blood Flow Metab 29(12):1903–1913. https://doi.org/10.1038/jcbfm.2009.102 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Liu J, Liu MC, Wang K (2008) Calpain in the CNS: from synaptic function to neurotoxicity. Sci Signal 1(14):re1CrossRefPubMedGoogle Scholar
  39. Liu J, Weiss HL, Rychahou P, Jackson LN, Evers BM, Gao T (2009) Loss of PHLPP expression in colon cancer: role in proliferation and tumorigenesis. Oncogene 28(7):994–1004CrossRefPubMedGoogle Scholar
  40. Liu S, Yin F, Zhang J, Qian Y (2014) The role of calpains in traumatic brain injury. Brain Inj 28(2):133–137CrossRefPubMedGoogle Scholar
  41. Mao L, Jia J, Zhou X, Xiao Y, Wang Y, Mao X, Zhen X, Guan Y, Alkayed NJ, Cheng J (2013) Delayed administration of a PTEN inhibitor BPV improves functional recovery after experimental stroke. Neuroscience 231:272–281. https://doi.org/10.1016/j.neuroscience.2012.11.050 CrossRefPubMedGoogle Scholar
  42. Markgraf CG, Velayo NL, Johnson MP, McCarty DR, Medhi S, Koehl JR, Chmielewski PA, Linnik MD (1998) Six-hour window of opportunity for calpain inhibition in focal cerebral ischemia in rats. Stroke 29(1):152–158CrossRefPubMedGoogle Scholar
  43. Masubuchi S, Gao T, O’Neill A, Eckel-Mahan K, Newton AC, Sassone-Corsi P (2010) Protein phosphatase PHLPP1 controls the light-induced resetting of the circadian clock. Proc Natl Acad Sci U S A 107(4):1642–1647. https://doi.org/10.1073/pnas.0910292107 CrossRefPubMedPubMedCentralGoogle Scholar
  44. Mingorance-Le Meur A, O’Connor TP (2009) Neurite consolidation is an active process requiring constant repression of protrusive activity. EMBO J 28(3):248–260CrossRefPubMedGoogle Scholar
  45. Monti B, Contestabile A (2000) Blockade of the NMDA receptor increases developmental apoptotic elimination of granule neurons and activates caspases in the rat cerebellum. Eur J Neurosci 12(9):3117–3123CrossRefPubMedGoogle Scholar
  46. Monti B, Marri L, Contestabile A (2002) NMDA receptor-dependent CREB activation in survival of cerebellar granule cells during in vivo and in vitro development. Eur J Neurosci 16(8):1490–1498CrossRefGoogle Scholar
  47. Moran J, Patel AJ (1989) Stimulation of the N-methyl-D-aspartate receptor promotes the biochemical differentiation of cerebellar granule neurons and not astrocytes. Brain Res 486(1):15–25CrossRefPubMedGoogle Scholar
  48. Papadia S, Stevenson P, Hardingham NR, Bading H, Hardingham GE (2005) Nuclear Ca2+ and the cAMP response element-binding protein family mediate a late phase of activity-dependent neuroprotection. J Neurosci 25(17):4279–4287CrossRefPubMedGoogle Scholar
  49. Papouin T, Oliet SH (2014) Organization, control and function of extrasynaptic NMDA receptors. Philos Trans R Soc B 369(1654):20130601CrossRefGoogle Scholar
  50. Paquet-Durand F, Johnson L, Ekström P (2007) Calpain activity in retinal degeneration. J Neurosci Res 85(4):693–702CrossRefPubMedGoogle Scholar
  51. Pennacchio LA, Bouley DM, Higgins KM, Scott MP, Noebels JL, Myers RM (1998) Progressive ataxia, myoclonic epilepsy and cerebellar apoptosis in cystatin B-deficient mice. Nat Genet 20(3):251–258. https://doi.org/10.1038/3059 CrossRefPubMedGoogle Scholar
  52. Perkinton MS, Ip J, Wood GL, Crossthwaite AJ, Williams RJ (2002) Phosphatidylinositol 3-kinase is a central mediator of NMDA receptor signalling to MAP kinase (Erk1/2), Akt/PKB and CREB in striatal neurones. J Neurochem 80(2):239–254CrossRefPubMedGoogle Scholar
  53. Perlmutter LS, Siman R, Gall C, Seubert P, Baudry M, Lynch G (1988) The ultrastructural localization of calcium-activated protease “calpain” in rat brain. Synapse 2(1):79–88CrossRefPubMedGoogle Scholar
  54. Saavedra A, Garcia-Martinez J, Xifro X, Giralt A, Torres-Peraza J, Canals J, Diaz-Hernandez M, Lucas J, Alberch J, Perez-Navarro E (2010) PH domain leucine-rich repeat protein phosphatase 1 contributes to maintain the activation of the PI3K/Akt pro-survival pathway in Huntington's disease striatum. Cell Death Differ 17(2):324–335CrossRefPubMedGoogle Scholar
  55. Schoch KM, Evans HN, Brelsfoard JM, Madathil SK, Takano J, Saido TC, Saatman KE (2012) Calpastatin overexpression limits calpain-mediated proteolysis and behavioral deficits following traumatic brain injury. Exp Neurol 236(2):371–382CrossRefPubMedPubMedCentralGoogle Scholar
  56. Shimazawa M, Suemori S, Inokuchi Y, Matsunaga N, Nakajima Y, Oka T, Yamamoto T, Hara H (2010) A novel calpain inhibitor, ((1S)-1-((((1S)-1-Benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-me thylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945), reduces murine retinal cell death in vitro and in vivo. J Pharmacol Exp Ther 332(2):380–387. https://doi.org/10.1124/jpet.109.156612 CrossRefPubMedGoogle Scholar
  57. Shimizu K, Okada M, Nagai K, Fukada Y (2003) Suprachiasmatic nucleus circadian oscillatory protein, a novel binding partner of K-Ras in the membrane rafts, negatively regulates MAPK pathway. J Biol Chem 278(17):14920–14925CrossRefPubMedGoogle Scholar
  58. Shimizu K, Phan T, Mansuy IM, Storm DR (2007) Proteolytic degradation of SCOP in the hippocampus contributes to activation of MAP kinase and memory. Cell 128(6):1219–1229CrossRefPubMedPubMedCentralGoogle Scholar
  59. Shmerling D, Hegyi I, Fischer M, Blattler T, Brandner S, Gotz J, Rulicke T, Flechsig E, Cozzio A, von Mering C, Hangartner C, Aguzzi A, Weissmann C (1998) Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions. Cell 93(2):203–214CrossRefPubMedGoogle Scholar
  60. Siklos M, BenAissa M, Thatcher GR (2015) Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors. Acta Pharm Sin B 5(6):506–519CrossRefPubMedPubMedCentralGoogle Scholar
  61. Simonson L, Baudry M, Siman R, Lynch G (1985) Regional distribution of soluble calcium activated proteinase activity in neonatal and adult rat brain. Brain Res 327(1–2):153–159CrossRefPubMedGoogle Scholar
  62. Soriano FX, Papadia S, Hofmann F, Hardingham NR, Bading H, Hardingham GE (2006) Preconditioning doses of NMDA promote neuroprotection by enhancing neuronal excitability. J Neurosci 26(17):4509–4518CrossRefPubMedPubMedCentralGoogle Scholar
  63. Steward O, Wallace CS (1995) mRNA distribution within dendrites: relationship to afferent innervation. J Neurobiol 26(3):447–459CrossRefPubMedGoogle Scholar
  64. Thompson SN, Carrico KM, Mustafa AG, Bains M, Hall ED (2010) A pharmacological analysis of the neuroprotective efficacy of the brain-and cell-permeable calpain inhibitor MDL-28170 in the mouse controlled cortical impact traumatic brain injury model. J Neurotrauma 27(12):2233–2243CrossRefPubMedPubMedCentralGoogle Scholar
  65. Tovar KR, Westbrook GL (1999) The incorporation of NMDA receptors with a distinct subunit composition at nascent hippocampal synapses in vitro. J Neurosci 19(10):4180–4188CrossRefPubMedGoogle Scholar
  66. Tsubokawa T, Solaroglu I, Yatsushige H, Cahill J, Yata K, Zhang JH (2006) Cathepsin and calpain inhibitor E64d attenuates matrix metalloproteinase-9 activity after focal cerebral ischemia in rats. Stroke 37(7):1888–1894. https://doi.org/10.1161/01.STR.0000227259.15506.24 CrossRefPubMedGoogle Scholar
  67. Vosler P, Brennan C, Chen J (2008) Calpain-mediated signaling mechanisms in neuronal injury and neurodegeneration. Mol Neurobiol 38(1):78–100CrossRefPubMedPubMedCentralGoogle Scholar
  68. Wang C-F, Huang Y-S (2012) Calpain 2 activated through N-methyl-D-aspartic acid receptor signaling cleaves CPEB3 and abrogates CPEB3-repressed translation in neurons. Mol Cell Biol 32(16):3321–3332CrossRefPubMedPubMedCentralGoogle Scholar
  69. Wang JT, Medress ZA, Barres BA (2012a) Axon degeneration: molecular mechanisms of a self-destruction pathway. J Cell Biol 196(1):7–18CrossRefPubMedPubMedCentralGoogle Scholar
  70. Wang Y-B, Wang J-J, Wang S-H, Liu S-S, Cao J-Y, Li X-M, Qiu S, Luo J-H (2012b) Adaptor protein APPL1 couples synaptic NMDA receptor with neuronal prosurvival phosphatidylinositol 3-kinase/Akt pathway. J Neurosci 32(35):11919–11929CrossRefPubMedGoogle Scholar
  71. Wang Y, Briz V, Chishti A, Bi X, Baudry M (2013) Distinct roles for mu-calpain and m-calpain in synaptic NMDAR-mediated neuroprotection and extrasynaptic NMDAR-mediated neurodegeneration. J Neurosci 33(48):18880–18892. https://doi.org/10.1523/JNEUROSCI.3293-13.2013 CrossRefPubMedPubMedCentralGoogle Scholar
  72. Wang Y, Zhu G, Briz V, Hsu YT, Bi X, Baudry M (2014) A molecular brake controls the magnitude of long-term potentiation. Nat Commun 5:3051. https://doi.org/10.1038/ncomms4051 CrossRefPubMedPubMedCentralGoogle Scholar
  73. Wang Y, Hersheson J, Lopez D, Hammer M, Liu Y, Lee KH, Pinto V, Seinfeld J, Wiethoff S, Sun J, Amouri R, Hentati F, Baudry N, Tran J, Singleton AB, Coutelier M, Brice A, Stevanin G, Durr A, Bi X, Houlden H, Baudry M (2016a) Defects in the CAPN1 gene result in alterations in cerebellar development and cerebellar ataxia in mice and humans. Cell Rep 16(1):79–91. https://doi.org/10.1016/j.celrep.2016.05.044 CrossRefPubMedPubMedCentralGoogle Scholar
  74. Wang Y, Lopez D, Davey PG, Cameron DJ, Nguyen K, Tran J, Marquez E, Liu Y, Bi X, Baudry M (2016b) Calpain-1 and calpain-2 play opposite roles in retinal ganglion cell degeneration induced by retinal ischemia/reperfusion injury. Neurobiol Dis 93:121–128. https://doi.org/10.1016/j.nbd.2016.05.007 CrossRefPubMedGoogle Scholar
  75. Wang, Y, Liu, Y, Lopez, D, Lee, M, Dayal, S, Hirtado, A, Bi, X and Baudry, M (2017) Protection against TBI-induced neuronal death with post-treatment with a selective calpain-2 inhibitor in mice. J Neurotrauma 34:1–13Google Scholar
  76. Xiong Y, Mahmood A, Chopp M (2013) Animal models of traumatic brain injury. Nat Rev Neurosci 14(2):128–142CrossRefPubMedPubMedCentralGoogle Scholar
  77. Xu J, Kurup P, Zhang Y, Goebel-Goody SM, Wu PH, Hawasli AH, Baum ML, Bibb JA, Lombroso PJ (2009) Extrasynaptic NMDA receptors couple preferentially to excitotoxicity via calpain-mediated cleavage of STEP. J Neurosci 29(29):9330–9343. https://doi.org/10.1523/JNEUROSCI.2212-09.2009 CrossRefPubMedPubMedCentralGoogle Scholar
  78. Yamaguchi A, Tamatani M, Matsuzaki H, Namikawa K, Kiyama H, Vitek MP, Mitsuda N, Tohyama M (2001) Akt activation protects hippocampal neurons from apoptosis by inhibiting transcriptional activity of p53. J Biol Chem 276(7):5256–5264CrossRefPubMedGoogle Scholar
  79. Yan X-X, Jeromin A (2012) Spectrin breakdown products (SBDPs) as potential biomarkers for neurodegenerative diseases. Curr Trans Geriatr Exp Gerontol Rep 1(2):85–93CrossRefGoogle Scholar
  80. Yildiz-Unal A, Korulu S, Karabay A (2015) Neuroprotective strategies against calpain-mediated neurodegeneration. Neuropsychiatr Dis Treat 11:297CrossRefPubMedPubMedCentralGoogle Scholar
  81. Zadran S, Jourdi H, Rostamiani K, Qin Q, Bi X, Baudry M (2010) Brain-derived neurotrophic factor and epidermal growth factor activate neuronal m-calpain via mitogen-activated protein kinase-dependent phosphorylation. J Neurosci 30(3):1086–1095CrossRefPubMedGoogle Scholar
  82. Zhou M, Baudry M (2006) Developmental changes in NMDA neurotoxicity reflect developmental changes in subunit composition of NMDA receptors. J Neurosci 26(11):2956–2963CrossRefPubMedGoogle Scholar
  83. Zhu G, Liu Y, Wang Y, Bi X, Baudry M (2015) Different patterns of electrical activity lead to long-term potentiation by activating different intracellular pathways. J Neurosci 35(2):621–633. https://doi.org/10.1523/JNEUROSCI.2193-14.2015 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Graduate College of Biomedical SciencesWestern University of Health SciencesPomonaUSA
  2. 2.College of Osteopathic Medicine of the PacificWestern University of Health SciencesPomonaUSA

Personalised recommendations