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Cell Cycle Activation and CNS Injury

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Abstract

Although traditionally it was believed that adult neurons have entered a permanent post-mitotic phase, the latest experimental data indicate that cell cycle constituents critically affect normal functions of the adult central nervous system (CNS), as well as contribute to the pathophysiology of both acute and chronic neurodegenerative disorders. Recent study has also suggested that cell cycle pathways are involved in mediating not only neuronal cell death but also glial changes which may play key roles in the pathophysiological mechanisms underlying acute and chronic neurodegenerative disorders. Therefore, therapies that inhibit cell cycle may have robust neuroprotective profiles, particularly after acute insults, by targeting multiple pathogenic mechanisms and could be useful clinically if used with a delivery focused on specific areas and of a limited duration.

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References

  • Adamec E, Vonsattel JP, Nixon RA (1999) DNA strand breaks in Alzheimer’s disease. Brain Res 849:67–77

    Article  PubMed  CAS  Google Scholar 

  • al-Ubaidi MR, Hollyfield JG, Overbeek PA, Baehr W (1992) Photoreceptor degeneration induced by the expression of simian virus 40 large tumor antigen in the retina of transgenic mice. Proc Natl Acad Sci USA 89:1194–1198

    Article  PubMed  CAS  Google Scholar 

  • Arendt T (2000) Alzheimer’s disease as a loss of differentiation control in a subset of neurons that retain immature features in the adult brain. Neurobiol Aging 21:783–796

    Article  PubMed  CAS  Google Scholar 

  • Arendt T (2001) Disturbance of neuronal plasticity is a critical pathogenetic event in Alzheimer’s disease. Int J Dev Neurosci 19:231–245

    Article  PubMed  CAS  Google Scholar 

  • Arendt T (2003) Synaptic plasticity and cell cycle activation in neurons are alternative effector pathways: the ‘Dr. Jekyll and Mr. Hyde concept’ of Alzheimer’s disease or the yin and yang of neuroplasticity. Prog Neurobiol 71:83–248

    Article  PubMed  Google Scholar 

  • Arendt T, Bruckner MK (2007) Linking cell-cycle dysfunction in Alzheimer’s disease to a failure of synaptic plasticity. Biochim Biophys Acta 1772:413–421

    PubMed  CAS  Google Scholar 

  • Arendt T, Holzer M, Grossmann A, Zedlick D, Bruckner MK (1995) Increased expression and subcellular translocation of the mitogen activated protein kinase kinase and mitogen-activated protein kinase in Alzheimer’s disease. Neuroscience 68:5–18

    Article  PubMed  CAS  Google Scholar 

  • Arendt T, Rodel L, Gartner U, Holzer M (1996) Expression of the cyclin-dependent kinase inhibitor p16 in Alzheimer’s disease. NeuroReport 7:3047–3049

    PubMed  CAS  Google Scholar 

  • Arendt T, Holzer M, Stobe A, Gartner U, Luth HJ, Bruckner MK, Ueberham U (2000) Activated mitogenic signaling induces a process of dedifferentiation in Alzheimer’s disease that eventually results in cell death. Ann NY Acad Sci 920:249–255

    PubMed  CAS  Google Scholar 

  • Askew DS, Ashmun RA, Simmons BC, Cleveland JL (1991) Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis. Oncogene 6:1915–1922

    PubMed  CAS  Google Scholar 

  • Bach S et al (2005) Roscovitine targets, protein kinases and pyridoxal kinase. J Biol Chem 280:31208–31219

    Article  PubMed  CAS  Google Scholar 

  • Bain J, McLauchlan H, Elliott M, Cohen P (2003) The specificities of protein kinase inhibitors: an update. Biochem J 371:199–204

    Article  PubMed  CAS  Google Scholar 

  • Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, Klevernic I, Arthur JS, Alessi DR, Cohen P (2007) The selectivity of protein kinase inhibitors: a further update. Biochem J 408:297–315

    Article  PubMed  CAS  Google Scholar 

  • Barzilai A, Biton S, Shiloh Y (2008) The role of the DNA damage response in neuronal development, organization and maintenance. DNA Repair (Amst) 7:1010–1027

    Article  CAS  Google Scholar 

  • Biswas SC, Greene LA (2002) Nerve growth factor (NGF) down-regulates the Bcl-2 homology 3 (BH3) domain-only protein Bim and suppresses its proapoptotic activity by phosphorylation. J Biol Chem 277:49511–49516

    Article  PubMed  CAS  Google Scholar 

  • Biswas SC, Liu DX, Greene LA (2005) Bim is a direct target of a neuronal E2F-dependent apoptotic pathway. J Neurosci 25:8349–8358

    Article  PubMed  CAS  Google Scholar 

  • Biswas SC, Shi Y, Sproul A, Greene LA (2007) Pro-apoptotic Bim induction in response to nerve growth factor deprivation requires simultaneous activation of three different death signaling pathways. J Biol Chem 282:29368–29374

    Article  PubMed  CAS  Google Scholar 

  • Brady HJ, Gil-Gomez G, Kirberg J, Berns AJ (1996) Bax alpha perturbs T cell development and affects cell cycle entry of T cells. EMBO J 15:6991–7001

    PubMed  CAS  Google Scholar 

  • Bravo R, Frank R, Blundell PA, Macdonald-Bravo H (1987) Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature 326:515–517

    Article  PubMed  CAS  Google Scholar 

  • Burns KA, Ayoub AE, Breunig JJ, Adhami F, Weng WL, Colbert MC, Rakic P, Kuan CY (2007) Nestin-CreER mice reveal DNA synthesis by nonapoptotic neurons following cerebral ischemia hypoxia. Cereb Cortex 17:2585–2592

    Article  PubMed  Google Scholar 

  • Byrnes KR, Faden AI (2007) Role of cell cycle proteins in CNS injury. Neurochem Res 32:1799–1807

    Article  PubMed  CAS  Google Scholar 

  • Byrnes KR, Stoica BA, Fricke S, Di Giovanni S, Faden AI (2007) Cell cycle activation contributes to post-mitotic cell death and secondary damage after spinal cord injury. Brain 130:2977–2992

    Article  PubMed  Google Scholar 

  • Carlson SL, Parrish ME, Springer JE, Doty K, Dossett L (1998) Acute inflammatory response in spinal cord following impact injury. Exp Neurol 151:77–88

    Article  PubMed  CAS  Google Scholar 

  • Cernak I, Stoica B, Byrnes KR, Di Giovanni S, Faden AI (2005) Role of the cell cycle in the pathobiology of central nervous system trauma. Cell Cycle 4:1286–1293

    PubMed  CAS  Google Scholar 

  • Chen Y, McPhie DL, Hirschberg J, Neve RL (2000) The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons. J Biol Chem 275:8929–8935

    Article  PubMed  CAS  Google Scholar 

  • Cicero S, Herrup K (2005) Cyclin-dependent kinase 5 is essential for neuronal cell cycle arrest and differentiation. J Neurosci 25:9658–9668

    Article  PubMed  CAS  Google Scholar 

  • Clarke AR, Maandag ER, van Roon M, van der Lugt NM, van der Valk M, Hooper ML, Berns A, te Riele H (1992) Requirement for a functional Rb-1 gene in murine development. Nature 359:328–330

    Article  PubMed  CAS  Google Scholar 

  • Colombel M, Olsson CA, Ng PY, Buttyan R (1992) Hormone-regulated apoptosis results from reentry of differentiated prostate cells onto a defective cell cycle. Cancer Res 52:4313–4319

    PubMed  CAS  Google Scholar 

  • Copani A, Condorelli F, Caruso A, Vancheri C, Sala A, Giuffrida Stella AM, Canonico PL, Nicoletti F, Sortino MA (1999) Mitotic signaling by beta-amyloid causes neuronal death. FASEB J 13:2225–2234

    PubMed  CAS  Google Scholar 

  • Copani A, Uberti D, Sortino MA, Bruno V, Nicoletti F, Memo M (2001) Activation of cell-cycle-associated proteins in neuronal death: a mandatory or dispensable path? Trends Neurosci 24:25–31

    Article  PubMed  CAS  Google Scholar 

  • Copani A, Sortino MA, Nicoletti F, Giuffrida SA (2002a) Alzheimer’s disease research enters a “new cycle”: how significant? Neurochem Res 27:173–176

    Article  PubMed  CAS  Google Scholar 

  • Copani A, Sortino MA, Caricasole A, Chiechio S, Chisari M, Battaglia G, Giuffrida-Stella AM, Vancheri C, Nicoletti F (2002b) Erratic expression of DNA polymerases by beta-amyloid causes neuronal death. FASEB J 16:2006–2008

    PubMed  CAS  Google Scholar 

  • Copani A, Hoozemans JJ, Caraci F, Calafiore M, Van Haastert ES, Veerhuis R, Rozemuller AJ, Aronica E, Sortino MA, Nicoletti F (2006) DNA polymerase-beta is expressed early in neurons of Alzheimer’s disease brain and is loaded into DNA replication forks in neurons challenged with beta-amyloid. J Neurosci 26:10949–10957

    Article  PubMed  CAS  Google Scholar 

  • Copani A, Caraci F, Hoozemans JJ, Calafiore M, Sortino MA, Nicoletti F (2007) The nature of the cell cycle in neurons: focus on a “non-canonical” pathway of DNA replication causally related to death. Biochim Biophys Acta 1772:409–412

    PubMed  CAS  Google Scholar 

  • Cornforth MN, Bedford JS (1985) On the nature of a defect in cells from individuals with ataxia-telangiectasia. Science 227:1589–1591

    Article  PubMed  CAS  Google Scholar 

  • de Castro Ribeiro M, Badaut J, Price M, Meins M, Bogousslavsky J, Monard D, Hirt L (2006) Thrombin in ischemic neuronal death. Exp Neurol 198:199–203

    Article  PubMed  CAS  Google Scholar 

  • DeGregori J (2002) The genetics of the E2F family of transcription factors: shared functions and unique roles. Biochim Biophys Acta 1602:131–150

    PubMed  CAS  Google Scholar 

  • Dhavan R, Tsai LH (2001) A decade of CDK5. Nat Rev Mol Cell Biol 2:749–759

    Article  PubMed  CAS  Google Scholar 

  • Dhavan R, Greer PL, Morabito MA, Orlando LR, Tsai LH (2002) The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2 +/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent manner. J Neurosci 22:7879–7891

    PubMed  CAS  Google Scholar 

  • Di Giovanni S, Knoblach SM, Brandoli C, Aden SA, Hoffman EP, Faden AI (2003) Gene profiling in spinal cord injury shows role of cell cycle in neuronal death. Ann Neurol 53:454–468

    Article  PubMed  CAS  Google Scholar 

  • Di Giovanni S, Movsesyan V, Ahmed F, Cernak I, Schinelli S, Stoica B, Faden AI (2005) Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury. Proc Natl Acad Sci USA 102:8333–8338

    Article  PubMed  CAS  Google Scholar 

  • Evan G, Littlewood T (1998) A matter of life and cell death. Science 281:1317–1322

    Article  PubMed  CAS  Google Scholar 

  • Faden AI (2002) Neuroprotection and traumatic brain injury: theoretical option or realistic proposition. Curr Opin Neurol 15:707–712

    Article  PubMed  Google Scholar 

  • Feddersen RM, Ehlenfeldt R, Yunis WS, Clark HB, Orr HT (1992) Disrupted cerebellar cortical development and progressive degeneration of Purkinje cells in SV40 T antigen transgenic mice. Neuron 9:955–966

    Article  PubMed  CAS  Google Scholar 

  • Ferguson KL, Vanderluit JL, Hebert JM, McIntosh WC, Tibbo E, MacLaurin JG, Park DS, Wallace VA, Vooijs M, McConnell SK, Slack RS (2002) Telencephalon-specific Rb knockouts reveal enhanced neurogenesis, survival and abnormal cortical development. EMBO J 21:3337–3346

    Article  PubMed  CAS  Google Scholar 

  • Frasca G, Carbonaro V, Merlo S, Copani A, Sortino MA (2008) Integrins mediate beta-amyloid-induced cell-cycle activation and neuronal death. J Neurosci Res 86:350–355

    Article  PubMed  CAS  Google Scholar 

  • Freeman RS, Estus S, Johnson EM Jr (1994) Analysis of cell cycle-related gene expression in postmitotic neurons: selective induction of cyclin D1 during programmed cell death. Neuron 12:343–355

    Article  PubMed  CAS  Google Scholar 

  • Gabbita SP, Lovell MA, Markesbery WR (1998) Increased nuclear DNA oxidation in the brain in Alzheimer’s disease. J Neurochem 71:2034–2040

    Article  PubMed  CAS  Google Scholar 

  • Gartner U, Holzer M, Arendt T (1999) Elevated expression of p21ras is an early event in Alzheimer’s disease and precedes neurofibrillary degeneration. Neuroscience 91:1–5

    Article  PubMed  CAS  Google Scholar 

  • Gilley J, Coffer PJ, Ham J (2003) FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons. J Cell Biol 162:613–622

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez YR, Zhang Y, Behzadpoor D, Cregan S, Bamforth S, Slack RS, Park DS (2008) CITED2 signals through peroxisome proliferator-activated receptor-gamma to regulate death of cortical neurons after DNA damage. J Neurosci 28:5559–5569

    Article  PubMed  CAS  Google Scholar 

  • Greene LA, Biswas SC, Liu DX (2004) Cell cycle molecules and vertebrate neuron death: E2F at the hub. Cell Death Differ 11:49–60

    Article  PubMed  CAS  Google Scholar 

  • Greene LA, Liu DX, Troy CM, Biswas SC (2007) Cell cycle molecules define a pathway required for neuron death in development and disease. Biochim Biophys Acta 1772:392–401

    PubMed  CAS  Google Scholar 

  • Hamdane M, Bretteville A, Sambo AV, Schindowski K, Begard S, Delacourte A, Bertrand P, Buee L (2005) p25/Cdk5-mediated retinoblastoma phosphorylation is an early event in neuronal cell death. J Cell Sci 118:1291–1298

    Article  PubMed  CAS  Google Scholar 

  • Hanawalt PC, Gee P, Ho L, Hsu RK, Kane CJ (1992) Genomic heterogeneity of DNA repair. Role in aging? Ann NY Acad Sci 663:17–25

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto M, Nitta A, Fukumitsu H, Nomoto H, Shen L, Furukawa S (2005) Inflammation-induced GDNF improves locomotor function after spinal cord injury. NeuroReport 16:99–102

    Article  PubMed  CAS  Google Scholar 

  • Hayes TE, Valtz NL, McKay RD (1991) Downregulation of CDC2 upon terminal differentiation of neurons. New Biol 3:259–269

    PubMed  CAS  Google Scholar 

  • Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA (2003) Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol 60:1119–1122

    Article  PubMed  Google Scholar 

  • Hellmich MR, Pant HC, Wada E, Battey JF (1992) Neuronal cdc2-like kinase: a cdc2-related protein kinase with predominantly neuronal expression. Proc Natl Acad Sci USA 89:10867–10871

    Article  PubMed  CAS  Google Scholar 

  • Herrup K, Busser JC (1995) The induction of multiple cell cycle events precedes target-related neuronal death. Development 121:2385–2395

    PubMed  CAS  Google Scholar 

  • Herrup K, Yang Y (2007) Cell cycle regulation in the postmitotic neuron: oxymoron or new biology? Nat Rev Neurosci 8:368–378

    Article  PubMed  CAS  Google Scholar 

  • Herrup K, Neve R, Ackerman SL, Copani A (2004) Divide and die: cell cycle events as triggers of nerve cell death. J Neurosci 24:9232–9239

    Article  PubMed  CAS  Google Scholar 

  • Herzog KH, Chong MJ, Kapsetaki M, Morgan JI, McKinnon PJ (1998) Requirement for Atm in ionizing radiation-induced cell death in the developing central nervous system. Science 280:1089–1091

    Article  PubMed  CAS  Google Scholar 

  • Hesdorffer DC, Ghajar J (2007) Marked improvement in adherence to traumatic brain injury guidelines in United States trauma centers. J Trauma 63:841–847 discussion 847–848

    Article  PubMed  Google Scholar 

  • Hilton GD, Stoica BA, Byrnes KR, Faden AI (2008) Roscovitine reduces neuronal loss, glial activation, and neurologic deficits after brain trauma. J Cereb Blood Flow Metab 28:1845–1859

    Article  PubMed  CAS  Google Scholar 

  • Hock BJ Jr, Lamb BT (2001) Transgenic mouse models of Alzheimer’s disease. Trends Genet 17:S7–S12

    Article  PubMed  CAS  Google Scholar 

  • Hoglinger GU, Breunig JJ, Depboylu C, Rouaux C, Michel PP, Alvarez-Fischer D, Boutillier AL, Degregori J, Oertel WH, Rakic P, Hirsch EC, Hunot S (2007) The pRb/E2F cell-cycle pathway mediates cell death in Parkinson’s disease. Proc Natl Acad Sci USA 104:3585–3590

    Article  PubMed  CAS  Google Scholar 

  • Holbrook NJ, Ikeyama S (2002) Age-related decline in cellular response to oxidative stress: links to growth factor signaling pathways with common defects. Biochem Pharmacol 64:999–1005

    Article  PubMed  CAS  Google Scholar 

  • Huang Z, Zang K, Reichardt LF (2005) The origin recognition core complex regulates dendrite and spine development in postmitotic neurons. J Cell Biol 170:527–535

    Article  PubMed  CAS  Google Scholar 

  • Ino H, Chiba T (2001) Cyclin-dependent kinase 4 and cyclin D1 are required for excitotoxin-induced neuronal cell death in vivo. J Neurosci 21:6086–6094

    PubMed  CAS  Google Scholar 

  • Iyirhiaro GO, Brust TB, Rashidian J, Galehdar Z, Osman A, Phillips M, Slack RS, Macvicar BA, Park DS (2008) Delayed combinatorial treatment with flavopiridol and minocycline provides longer term protection for neuronal soma but not dendrites following global ischemia. J Neurochem 105:703–713

    Article  PubMed  CAS  Google Scholar 

  • Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA, Weinberg RA (1992) Effects of an Rb mutation in the mouse. Nature 359:295–300

    Article  PubMed  CAS  Google Scholar 

  • Jin K, Wang X, Xie L, Mao XO, Zhu W, Wang Y, Shen J, Mao Y, Banwait S, Greenberg DA (2006) Evidence for stroke-induced neurogenesis in the human brain. Proc Natl Acad Sci USA 103:13198–13202

    Article  PubMed  CAS  Google Scholar 

  • Jordan-Sciutto KL, Malaiyandi LM, Bowser R (2002) Altered distribution of cell cycle transcriptional regulators during Alzheimer disease. J Neuropathol Exp Neurol 61:358–367

    PubMed  CAS  Google Scholar 

  • Katchanov J, Harms C, Gertz K, Hauck L, Waeber C, Hirt L, Priller J, von Harsdorf R, Bruck W, Hortnagl H, Dirnagl U, Bhide PG, Endres M (2001) Mild cerebral ischemia induces loss of cyclin-dependent kinase inhibitors and activation of cell cycle machinery before delayed neuronal cell death. J Neurosci 21:5045–5053

    PubMed  CAS  Google Scholar 

  • Kawauchi T, Chihama K, Nabeshima Y, Hoshino M (2006) Cdk5 phosphorylates and stabilizes p27kip1 contributing to actin organization and cortical neuronal migration. Nat Cell Biol 8:17–26

    Article  PubMed  CAS  Google Scholar 

  • Kim SU, de Vellis J (2005) Microglia in health and disease. J Neurosci Res 81:302–313

    Article  PubMed  CAS  Google Scholar 

  • Kim D, Frank CL, Dobbin MM, Tsunemoto RK, Tu W, Peng PL, Guan JS, Lee BH, Moy LY, Giusti P, Broodie N, Mazitschek R, Delalle I, Haggarty SJ, Neve RL, Lu Y, Tsai LH (2008) Deregulation of HDAC1 by p25/Cdk5 in neurotoxicity. Neuron 60:803–817

    Article  PubMed  CAS  Google Scholar 

  • Kingsbury MA, Friedman B, McConnell MJ, Rehen SK, Yang AH, Kaushal D, Chun J (2005) Aneuploid neurons are functionally active and integrated into brain circuitry. Proc Natl Acad Sci USA 102:6143–6147

    Article  PubMed  CAS  Google Scholar 

  • Kingsbury MA, Yung YC, Peterson SE, Westra JW, Chun J (2006) Aneuploidy in the normal and diseased brain. Cell Mol Life Sci 63:2626–2641

    Article  PubMed  CAS  Google Scholar 

  • Konishi Y, Bonni A (2003) The E2F-Cdc2 cell-cycle pathway specifically mediates activity deprivation-induced apoptosis of postmitotic neurons. J Neurosci 23:1649–1658

    PubMed  CAS  Google Scholar 

  • Kranenburg O, van der Eb AJ, Zantema A (1996) Cyclin D1 is an essential mediator of apoptotic neuronal cell death. EMBO J 15:46–54

    PubMed  CAS  Google Scholar 

  • Kriz J, Nguyen MD, Julien JP (2002) Minocycline slows disease progression in a mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 10:268–278

    Article  PubMed  CAS  Google Scholar 

  • Kriz J, Gowing G, Julien JP (2003) Efficient three-drug cocktail for disease induced by mutant superoxide dismutase. Ann Neurol 53:429–436

    Article  PubMed  CAS  Google Scholar 

  • Kruman II (2004) Why do neurons enter the cell cycle? Cell Cycle 3:769–773

    PubMed  CAS  Google Scholar 

  • Kruman II, Schwartz EI (2008) DNA damage response and neuroprotection. Front Biosci 13:2504–2515

    Article  PubMed  CAS  Google Scholar 

  • Kruman II, Wersto RP, Cardozo-Pelaez F, Smilenov L, Chan SL, Chrest FJ, Emokpae R Jr, Gorospe M, Mattson MP (2004) Cell cycle activation linked to neuronal cell death initiated by DNA damage. Neuron 41:549–561

    Article  PubMed  CAS  Google Scholar 

  • Kuan CY, Schloemer AJ, Lu A, Burns KA, Weng WL, Williams MT, Strauss KI, Vorhees CV, Flavell RA, Davis RJ, Sharp FR, Rakic P (2004) Hypoxia-ischemia induces DNA synthesis without cell proliferation in dying neurons in adult rodent brain. J Neurosci 24:10763–10772

    Article  PubMed  CAS  Google Scholar 

  • Lai AY, Todd KG (2008) Differential regulation of trophic and proinflammatory microglial effectors is dependent on severity of neuronal injury. Glia 56:259–270

    Article  PubMed  Google Scholar 

  • Lam LT, Pickeral OK, Peng AC, Rosenwald A, Hurt EM, Giltnane JM, Averett LM, Zhao H, Davis RE, Sathyamoorthy M, Wahl LM, Harris ED, Mikovits JA, Monks AP, Hollingshead MG, Sausville EA, Staudt LM (2001) Genomic-scale measurement of mRNA turnover and the mechanisms of action of the anti-cancer drug flavopiridol. Genome Biol 2:1–11

    Article  Google Scholar 

  • Lan J, Henshall DC, Simon RP, Chen J (2000) Formation of the base modification 8-hydroxyl-2’-deoxyguanosine and DNA fragmentation following seizures induced by systemic kainic acid in the rat. J Neurochem 74:302–309

    Article  PubMed  CAS  Google Scholar 

  • LeCouter JE, Kablar B, Whyte PF, Ying C, Rudnicki MA (1998a) Strain-dependent embryonic lethality in mice lacking the retinoblastoma-related p130 gene. Development 125:4669–4679

    PubMed  CAS  Google Scholar 

  • LeCouter JE, Kablar B, Hardy WR, Ying C, Megeney LA, May LL, Rudnicki MA (1998b) Strain-dependent myeloid hyperplasia, growth deficiency, and accelerated cell cycle in mice lacking the Rb-related p107 gene. Mol Cell Biol 18:7455–7465

    PubMed  CAS  Google Scholar 

  • Ledesma MD, Correas I, Avila J, Diaz-Nido J (1992) Implication of brain cdc2 and MAP2 kinases in the phosphorylation of tau protein in Alzheimer’s disease. FEBS Lett 308:218–224

    Article  PubMed  CAS  Google Scholar 

  • Lee EY, Chang CY, Hu N, Wang YC, Lai CC, Herrup K, Lee WH, Bradley A (1992) Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. Nature 359:288–294

    Article  PubMed  CAS  Google Scholar 

  • Lee KY, Helbing CC, Choi KS, Johnston RN, Wang JH (1997) Neuronal Cdc2-like kinase (Nclk) binds and phosphorylates the retinoblastoma protein. J Biol Chem 272:5622–5626

    Article  PubMed  CAS  Google Scholar 

  • Li Z, David G, Hung KW, DePinho RA, Fu AK, Ip NY (2004) Cdk5/p35 phosphorylates mSds3 and regulates mSds3-mediated repression of transcription. J Biol Chem 279:54438–54444

    Article  PubMed  CAS  Google Scholar 

  • Liu DX, Greene LA (2001) Regulation of neuronal survival and death by E2F-dependent gene repression and derepression. Neuron 32:425–438

    Article  PubMed  CAS  Google Scholar 

  • Liu DX, Biswas SC, Greene LA (2004) B-myb and C-myb play required roles in neuronal apoptosis evoked by nerve growth factor deprivation and DNA damage. J Neurosci 24:8720–8725

    Article  PubMed  CAS  Google Scholar 

  • Lodish HF (2008) Molecular cell biology, 6th edn. W.H. Freeman, New York

    Google Scholar 

  • Lundberg AS, Weinberg RA (1998) Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol Cell Biol 18:753–761

    PubMed  CAS  Google Scholar 

  • MacPherson D, Sage J, Crowley D, Trumpp A, Bronson RT, Jacks T (2003) Conditional mutation of Rb causes cell cycle defects without apoptosis in the central nervous system. Mol Cell Biol 23:1044–1053

    Article  PubMed  CAS  Google Scholar 

  • Maeda M, Ampo K, Kiryu-Seo S, Konishi H, Ohba N, Kadono C, Kiyama H (2005) The p53-independent nuclear translocation of cyclin G1 in degenerating neurons by ischemic and traumatic insults. Exp Neurol 193:350–360

    Article  PubMed  CAS  Google Scholar 

  • Martindale JL, Holbrook NJ (2002) Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol 192:1–15

    Article  PubMed  CAS  Google Scholar 

  • Mattson MP (2000) Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol 1:120–129

    Article  PubMed  CAS  Google Scholar 

  • McGeer PL, Klegeris A, Walker DG, Yasuhara O, McGeer EG (1994) Pathological proteins in senile plaques. Tohoku J Exp Med 174:269–277

    Article  PubMed  CAS  Google Scholar 

  • McPhie DL, Coopersmith R, Hines-Peralta A, Chen Y, Ivins KJ, Manly SP, Kozlowski MR, Neve KA, Neve RL (2003) DNA synthesis and neuronal apoptosis caused by familial Alzheimer disease mutants of the amyloid precursor protein are mediated by the p21 activated kinase PAK3. J Neurosci 23:6914–6927

    PubMed  CAS  Google Scholar 

  • McShea A, Harris PL, Webster KR, Wahl AF, Smith MA (1997) Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer’s disease. Am J Pathol 150:1933–1939

    PubMed  CAS  Google Scholar 

  • Meijer L, Raymond E (2003) Roscovitine and other purines as kinase inhibitors. From starfish oocytes to clinical trials. Acc Chem Res 36:417–425

    Article  PubMed  CAS  Google Scholar 

  • Meijer L, Borgne A, Mulner O, Chong JP, Blow JJ, Inagaki N, Inagaki M, Delcros JG, Moulinoux JP (1997) Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem 243:527–536

    Article  PubMed  CAS  Google Scholar 

  • Meikrantz W, Gisselbrecht S, Tam SW, Schlegel R (1994) Activation of cyclin A-dependent protein kinases during apoptosis. Proc Natl Acad Sci USA 91:3754–3758

    Article  PubMed  CAS  Google Scholar 

  • Monaco EA 3rd, Beaman-Hall CM, Mathur A, Vallano ML (2004) Roscovitine, olomoucine, purvalanol: inducers of apoptosis in maturing cerebellar granule neurons. Biochem Pharmacol 67:1947–1964

    Article  PubMed  CAS  Google Scholar 

  • Morioka T, Kalehua AN, Streit WJ (1991) The microglial reaction in the rat dorsal hippocampus following transient forebrain ischemia. J Cereb Blood Flow Metab 11:966–973

    PubMed  CAS  Google Scholar 

  • Nagayama T, Lan J, Henshall DC, Chen D, O’Horo C, Simon RP, Chen J (2000) Induction of oxidative DNA damage in the peri-infarct region after permanent focal cerebral ischemia. J Neurochem 75:1716–1728

    Article  PubMed  CAS  Google Scholar 

  • Nagy Z, Esiri MM, Smith AD (1997) Expression of cell division markers in the hippocampus in Alzheimer's disease and other neurodegenerative conditions. Acta Neuropathol 93:294–300

    Article  PubMed  CAS  Google Scholar 

  • Nahle Z, Polakoff J, Davuluri RV, McCurrach ME, Jacobson MD, Narita M, Zhang MQ, Lazebnik Y, Bar-Sagi D, Lowe SW (2002) Direct coupling of the cell cycle and cell death machinery by E2F. Nat Cell Biol 4:859–864

    Article  PubMed  CAS  Google Scholar 

  • Newcomb EW (2004) Flavopiridol: pleiotropic biological effects enhance its anti-cancer activity. Anticancer Drugs 15:411–419

    Article  PubMed  CAS  Google Scholar 

  • Nguyen MD, Boudreau M, Kriz J, Couillard-Despres S, Kaplan DR, Julien JP (2003) Cell cycle regulators in the neuronal death pathway of amyotrophic lateral sclerosis caused by mutant superoxide dismutase 1. J Neurosci 23:2131–2140

    PubMed  CAS  Google Scholar 

  • Nieto-Sampedro M (1999) Neurite outgrowth inhibitors in gliotic tissue. Adv Exp Med Biol 468:207–224

    PubMed  CAS  Google Scholar 

  • Ogawa O, Zhu X, Lee HG, Raina A, Obrenovich ME, Bowser R, Ghanbari HA, Castellani RJ, Perry G, Smith MA (2003) Ectopic localization of phosphorylated histone H3 in Alzheimer’s disease: a mitotic catastrophe? Acta Neuropathol 105:524–528

    PubMed  CAS  Google Scholar 

  • Okamoto T, Yamamura K, Hino O (1999) The mouse interferon-gamma transgene chronic hepatitis model (Review). Int J Mol Med 3:517–520

    PubMed  CAS  Google Scholar 

  • Okano HJ, Pfaff DW, Gibbs RB (1993) RB and Cdc2 expression in brain: correlations with 3H-thymidine incorporation and neurogenesis. J Neurosci 13:2930–2938

    PubMed  CAS  Google Scholar 

  • Osheroff WP, Jung HK, Beard WA, Wilson SH, Kunkel TA (1999) The fidelity of DNA polymerase beta during distributive and processive DNA synthesis. J Biol Chem 274:3642–3650

    Article  PubMed  CAS  Google Scholar 

  • Padmanabhan J, Park DS, Greene LA, Shelanski ML (1999) Role of cell cycle regulatory proteins in cerebellar granule neuron apoptosis. J Neurosci 19:8747–8756

    PubMed  CAS  Google Scholar 

  • Park DS, Morris EJ, Greene LA, Geller HM (1997a) G1/S cell cycle blockers and inhibitors of cyclin-dependent kinases suppress camptothecin-induced neuronal apoptosis. J Neurosci 17:1256–1270

    PubMed  CAS  Google Scholar 

  • Park DS, Levine B, Ferrari G, Greene LA (1997b) Cyclin dependent kinase inhibitors and dominant negative cyclin dependent kinase 4 and 6 promote survival of NGF-deprived sympathetic neurons. J Neurosci 17:8975–8983

    PubMed  CAS  Google Scholar 

  • Park DS, Obeidat A, Giovanni A, Greene LA (2000a) Cell cycle regulators in neuronal death evoked by excitotoxic stress: implications for neurodegeneration and its treatment. Neurobiol Aging 21:771–781

    Article  PubMed  CAS  Google Scholar 

  • Park DS, Morris EJ, Bremner R, Keramaris E, Padmanabhan J, Rosenbaum M, Shelanski ML, Geller HM, Greene LA (2000b) Involvement of retinoblastoma family members and E2F/DP complexes in the death of neurons evoked by DNA damage. J Neurosci 20:3104–3114

    PubMed  CAS  Google Scholar 

  • Pelegri C, Duran-Vilaregut J, del Valle J, Crespo-Biel N, Ferrer I, Pallas M, Camins A, Vilaplana J (2008) Cell cycle activation in striatal neurons from Huntington’s disease patients and rats treated with 3-nitropropionic acid. Int J Dev Neurosci 26:665–671

    Article  PubMed  CAS  Google Scholar 

  • Petersen RC (2000) Aging, mild cognitive impairment, and Alzheimer’s disease. Neurol Clin 18:789–806

    Article  PubMed  CAS  Google Scholar 

  • Qu D, Rashidian J, Mount MP, Aleyasin H, Parsanejad M, Lira A, Haque E, Zhang Y, Callaghan S, Daigle M, Rousseaux MW, Slack RS, Albert PR, Vincent I, Woulfe JM, Park DS (2007) Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson’s disease. Neuron 55:37–52

    Article  PubMed  CAS  Google Scholar 

  • Raina AK, Zhu X, Rottkamp CA, Monteiro M, Takeda A, Smith MA (2000) Cyclin’ toward dementia: cell cycle abnormalities and abortive oncogenesis in Alzheimer disease. J Neurosci Res 61:128–133

    Article  PubMed  CAS  Google Scholar 

  • Ranganathan S, Bowser R (2003) Alterations in G(1) to S phase cell-cycle regulators during amyotrophic lateral sclerosis. Am J Pathol 162:823–835

    PubMed  CAS  Google Scholar 

  • Rao HV, Thirumangalakudi L, Desmond P, Grammas P (2007) Cyclin D1, cdk4, and Bim are involved in thrombin-induced apoptosis in cultured cortical neurons. J Neurochem 101:498–505

    Article  PubMed  CAS  Google Scholar 

  • Rashidian J, Iyirhiaro G, Aleyasin H, Rios M, Vincent I, Callaghan S, Bland RJ, Slack RS, During MJ, Park DS (2005) Multiple cyclin-dependent kinases signals are critical mediators of ischemia/hypoxic neuronal death in vitro and in vivo. Proc Natl Acad Sci USA 102:14080–14085

    Article  PubMed  CAS  Google Scholar 

  • Rashidian J, Iyirhiaro GO, Park DS (2007) Cell cycle machinery and stroke. Biochim Biophys Acta 1772:484–493

    PubMed  CAS  Google Scholar 

  • Rehen SK, Yung YC, McCreight MP, Kaushal D, Yang AH, Almeida BS, Kingsbury MA, Cabral KM, McConnell MJ, Anliker B, Fontanoz M, Chun J (2005) Constitutional aneuploidy in the normal human brain. J Neurosci 25:2176–2180

    Article  PubMed  CAS  Google Scholar 

  • Rideout HJ, Wang Q, Park DS, Stefanis L (2003) Cyclin-dependent kinase activity is required for apoptotic death but not inclusion formation in cortical neurons after proteasomal inhibition. J Neurosci 23:1237–1245

    PubMed  CAS  Google Scholar 

  • Rogove AD, Lu W, Tsirka SE (2002) Microglial activation and recruitment, but not proliferation, suffice to mediate neurodegeneration. Cell Death Differ 9:801–806

    Article  PubMed  CAS  Google Scholar 

  • Rolig RL, McKinnon PJ (2000) Linking DNA damage and neurodegeneration. Trends Neurosci 23:417–424

    Article  PubMed  CAS  Google Scholar 

  • Romito-DiGiacomo RR, Menegay H, Cicero SA, Herrup K (2007) Effects of Alzheimer’s disease on different cortical layers: the role of intrinsic differences in Abeta susceptibility. J Neurosci 27:8496–8504

    Article  PubMed  CAS  Google Scholar 

  • Rutland-Brown W, Langlois JA, Thomas KE, Xi YL (2006) Incidence of traumatic brain injury in the United States, 2003. J Head Trauma Rehabil 21:544–548

    Article  PubMed  Google Scholar 

  • Sakurai M, Hayashi T, Abe K, Itoyama Y, Tabayashi K, Rosenblum WI (2000) Cyclin D1 and Cdk4 protein induction in motor neurons after transient spinal cord ischemia in rabbits. Stroke 31:200–207

    PubMed  CAS  Google Scholar 

  • Sausville EA (2002) Complexities in the development of cyclin-dependent kinase inhibitor drugs. Trends Mol Med 8:S32–S37

    Article  PubMed  CAS  Google Scholar 

  • Sayre LM, Smith MA, Perry G (2001) Chemistry and biochemistry of oxidative stress in neurodegenerative disease. Curr Med Chem 8:721–738

    PubMed  CAS  Google Scholar 

  • Schmetsdorf S, Gartner U, Arendt T (2007) Constitutive expression of functionally active cyclin-dependent kinases and their binding partners suggests noncanonical functions of cell cycle regulators in differentiated neurons. Cereb Cortex 17:1821–1829

    Article  PubMed  Google Scholar 

  • Schwartz EI, Smilenov LB, Price MA, Osredkar T, Baker RA, Ghosh S, Shi FD, Vollmer TL, Lencinas A, Stearns DM, Gorospe M, Kruman II (2007) Cell cycle activation in postmitotic neurons is essential for DNA repair. Cell Cycle 6:318–329

    PubMed  CAS  Google Scholar 

  • Seo HR, Lee DH, Lee HJ, Baek M, Bae S, Soh JW, Lee SJ, Kim J, Lee YS (2006) Cyclin G1 overcomes radiation-induced G2 arrest and increases cell death through transcriptional activation of cyclin B1. Cell Death Differ 13:1475–1484

    Article  PubMed  CAS  Google Scholar 

  • Shan B, Lee WH (1994) Deregulated expression of E2F–1 induces S-phase entry and leads to apoptosis. Mol Cell Biol 14:8166–8173

    PubMed  CAS  Google Scholar 

  • Sherr CJ (1993) Mammalian G1 cyclins. Cell 73:1059–1065

    Article  PubMed  CAS  Google Scholar 

  • Silver J, Miller JH (2004) Regeneration beyond the glial scar. Nat Rev Neurosci 5:146–156

    Article  PubMed  CAS  Google Scholar 

  • Strachan GD, Koike MA, Siman R, Hall DJ, Jordan-Sciutto KL (2005) E2F1 induces cell death, calpain activation, and MDMX degradation in a transcription independent manner implicating a novel role for E2F1 in neuronal loss in SIV encephalitis. J Cell Biochem 96:728–740

    Article  PubMed  CAS  Google Scholar 

  • Strazza M, Luddi A, Brogi A, Carbone M, Riccio M, Santi S, Melli M, Costantino-Ceccarini E (2004) Activation of cell cycle regulatory proteins in the apoptosis of terminally differentiated oligodendrocytes. Neurochem Res 29:923–931

    Article  PubMed  CAS  Google Scholar 

  • Sultana R, Butterfield DA (2007) Regional expression of key cell cycle proteins in brain from subjects with amnestic mild cognitive impairment. Neurochem Res 32:655–662

    Article  PubMed  CAS  Google Scholar 

  • Takuma K, Baba A, Matsuda T (2004) Astrocyte apoptosis: implications for neuroprotection. Prog Neurobiol 72:111–127

    Article  PubMed  CAS  Google Scholar 

  • Tamatani M, Che YH, Matsuzaki H, Ogawa S, Okado H, Miyake S, Mizuno T, Tohyama M (1999) Tumor necrosis factor induces Bcl-2 and Bcl-x expression through NFkappaB activation in primary hippocampal neurons. J Biol Chem 274:8531–8538

    Article  PubMed  CAS  Google Scholar 

  • Tian DS, Yu ZY, Xie MJ, Bu BT, Witte OW, Wang W (2006) Suppression of astroglial scar formation and enhanced axonal regeneration associated with functional recovery in a spinal cord injury rat model by the cell cycle inhibitor olomoucine. J Neurosci Res 84:1053–1063

    Article  PubMed  CAS  Google Scholar 

  • Tian DS, Dong Q, Pan DJ, He Y, Yu ZY, Xie MJ, Wang W (2007a) Attenuation of astrogliosis by suppressing of microglial proliferation with the cell cycle inhibitor olomoucine in rat spinal cord injury model. Brain Res 1154:206–214

    Article  PubMed  CAS  Google Scholar 

  • Tian DS, Xie MJ, Yu ZY, Zhang Q, Wang YH, Chen B, Chen C, Wang W (2007b) Cell cycle inhibition attenuates microglia induced inflammatory response and alleviates neuronal cell death after spinal cord injury in rats. Brain Res 1135:177–185

    Article  PubMed  CAS  Google Scholar 

  • Tian B, Yang Q, Mao Z (2009) Phosphorylation of ATM by Cdk5 mediates DNA damage signalling and regulates neuronal death. Nat Cell Biol 11:211–218

    Article  PubMed  CAS  Google Scholar 

  • Tikka T, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J (2001) Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci 21:2580–2588

    PubMed  CAS  Google Scholar 

  • Timsit S, Rivera S, Ouaghi P, Guischard F, Tremblay E, Ben-Ari Y, Khrestchatisky M (1999) Increased cyclin D1 in vulnerable neurons in the hippocampus after ischaemia and epilepsy: a modulator of in vivo programmed cell death? Eur J NeuroSci 11:263–278

    Article  PubMed  CAS  Google Scholar 

  • Tomasevic G, Kamme F, Wieloch T (1998) Changes in proliferating cell nuclear antigen, a protein involved in DNA repair, in vulnerable hippocampal neurons following global cerebral ischemia. Brain Res Mol Brain Res 60:168–176

    Article  PubMed  CAS  Google Scholar 

  • Ucker DS (1991) Death by suicide: one way to go in mammalian cellular development? New Biol 3:103–109

    PubMed  CAS  Google Scholar 

  • Ueberham U, Arendt T (2005) The expression of cell cycle proteins in neurons and its relevance for Alzheimer’s disease. Curr Drug Targets CNS Neurol Disord 4:293–306

    Article  PubMed  CAS  Google Scholar 

  • van Lookeren Campagne M, Gill R (1998) Increased expression of cyclin G1 and p21 WAF1/CIP1 in neurons following transient forebrain ischemia: comparison with early DNA damage. J Neurosci Res 53:279–296

    Article  PubMed  Google Scholar 

  • Varvel NH, Bhaskar K, Patil AR, Pimplikar SW, Herrup K, Lamb BT (2008) Abeta oligomers induce neuronal cell cycle events in Alzheimer’s disease. J Neurosci 28:10786–10793

    Article  PubMed  CAS  Google Scholar 

  • Verdaguer E, Garcia-Jorda E, Canudas AM, Dominguez E, Jimenez A, Pubill D, Escubedo E, Pallas JC, Camins A (2002) Kainic acid-induced apoptosis in cerebellar granule neurons: an attempt at cell cycle re-entry. NeuroReport 13:413–416

    Article  PubMed  CAS  Google Scholar 

  • Vincent I, Bu B, Hudson K, Husseman J, Nochlin D, Jin L (2001) Constitutive Cdc25B tyrosine phosphatase activity in adult brain neurons with M phase-type alterations in Alzheimer’s disease. Neuroscience 105:639–650

    Article  PubMed  CAS  Google Scholar 

  • Vincent I, Jicha G, Rosado M, Dickson DW (1997) Aberrant expression of mitotic cdc2/cyclin B1 kinase in degenerating neurons of Alzheimer's disease brain. J Neurosci 17:3588–3598

    PubMed  CAS  Google Scholar 

  • Wallace DM, Cotter TG (2008) Histone deacetylase activity in conjunction with E2F–1 and p53 regulates Apaf-1 expression in 661 W cells and the retina. J Neurosci Res 87:887–905

    Article  CAS  Google Scholar 

  • Walsh MJ, Shue G, Spidoni K, Kapoor A (1995) E2F–1 and a cyclin-like DNA repair enzyme, uracil-DNA glycosylase, provide evidence for an autoregulatory mechanism for transcription. J Biol Chem 270:5289–5298

    Article  PubMed  CAS  Google Scholar 

  • Wang F, Corbett D, Osuga H, Osuga S, Ikeda JE, Slack RS, Hogan MJ, Hakim AM, Park DS (2002) Inhibition of cyclin-dependent kinases improves CA1 neuronal survival and behavioral performance after global ischemia in the rat. J Cereb Blood Flow Metab 22:171–182

    Article  PubMed  CAS  Google Scholar 

  • Wang L, Wang R, Herrup K (2007a) E2F1 works as a cell cycle suppressor in mature neurons. J Neurosci 27:12555–12564

    Article  PubMed  CAS  Google Scholar 

  • Wang Q, Tang XN, Yenari MA (2007b) The inflammatory response in stroke. J Neuroimmunol 184:53–68

    Article  PubMed  CAS  Google Scholar 

  • Wei Y, Yu L, Bowen J, Gorovsky MA, Allis CD (1999) Phosphorylation of histone H3 is required for proper chromosome condensation and segregation. Cell 97:99–109

    Article  PubMed  CAS  Google Scholar 

  • Wen Y, Yang S, Liu R, Brun-Zinkernagel AM, Koulen P, Simpkins JW (2004) Transient cerebral ischemia induces aberrant neuronal cell cycle re-entry and Alzheimer’s disease-like tauopathy in female rats. J Biol Chem 279:22684–22692

    Article  PubMed  CAS  Google Scholar 

  • Wyllie AH, Kerr JF, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306

    Article  PubMed  CAS  Google Scholar 

  • Yakovlev AG, Faden AI (2004) Mechanisms of neural cell death: implications for development of neuroprotective treatment strategies. NeuroRX 1:5–16

    Article  PubMed  Google Scholar 

  • Yang Y, Herrup K (2005) Loss of neuronal cell cycle control in ataxia-telangiectasia: a unified disease mechanism. J Neurosci 25:2522–2529

    Article  PubMed  CAS  Google Scholar 

  • Yang Y, Herrup K (2007) Cell division in the CNS: protective response or lethal event in post-mitotic neurons? Biochim Biophys Acta 1772:457–466

    PubMed  CAS  Google Scholar 

  • Yang Y, Geldmacher DS, Herrup K (2001) DNA replication precedes neuronal cell death in Alzheimer’s disease. J Neurosci 21:2661–2668

    PubMed  CAS  Google Scholar 

  • Yang Y, Mufson EJ, Herrup K (2003) Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer’s disease. J Neurosci 23:2557–2563

    PubMed  CAS  Google Scholar 

  • Yang Y, Varvel NH, Lamb BT, Herrup K (2006) Ectopic cell cycle events link human Alzheimer’s disease and amyloid precursor protein transgenic mouse models. J Neurosci 26:775–784

    Article  PubMed  CAS  Google Scholar 

  • Zawadzka M, Kaminska B (2003) Immunosuppressant FK506 affects multiple signaling pathways and modulates gene expression in astrocytes. Mol Cell Neurosci 22:202–209

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Herrup K (2008) Cdk5 and the non-catalytic arrest of the neuronal cell cycle. Cell Cycle 7:3487–3490

    PubMed  CAS  Google Scholar 

  • Zhang Y, Qu D, Morris EJ, O’Hare MJ, Callaghan SM, Slack RS, Geller HM, Park DS (2006) The Chk1/Cdc25A pathway as activators of the cell cycle in neuronal death induced by camptothecin. J Neurosci 26:8819–8828

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Cicero SA, Wang L, Romito-Digiacomo RR, Yang Y, Herrup K (2008) Nuclear localization of Cdk5 is a key determinant in the postmitotic state of neurons. Proc Natl Acad Sci U S A 105:8772–8777

    Article  PubMed  CAS  Google Scholar 

  • Zhu Z, Zhang Q, Yu Z, Zhang L, Tian D, Zhu S, Bu B, Xie M, Wang W (2007) Inhibiting cell cycle progression reduces reactive astrogliosis initiated by scratch injury in vitro and by cerebral ischemia in vivo. Glia 55:546–558

    Article  PubMed  Google Scholar 

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  1. Department of Neuroscience, Georgetown University School of Medicine, Research Building, Room WG18, 3970 Reservoir Rd, NW, Washington, DC, 20057, USA

    Bogdan A. Stoica, Kimberly R. Byrnes & Alan I. Faden

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  1. Bogdan A. Stoica
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Stoica, B.A., Byrnes, K.R. & Faden, A.I. Cell Cycle Activation and CNS Injury. Neurotox Res 16, 221–237 (2009). https://doi.org/10.1007/s12640-009-9050-0

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