[en] A persistent dogma in neuroscience supported the idea that terminally differentiated neurons permanently withdraw from the cell cycle. However, since the late 1990s, several studies have shown that cell cycle proteins are expressed in post-mitotic neurons under physiological conditions, indicating that the cell cycle machinery is not restricted to proliferating cells. Moreover, many studies have highlighted a clear link between cell cycle-related proteins and neurological disorders, particularly relating to apoptosis-induced neuronal death. Indeed, cell cycle-related proteins can be upregulated or overactivated in post-mitotic neurons in case of acute or degenerative central nervous system disease. Given the considerable lack of effective treatments for age-related neurological disorders, new therapeutic approaches targeting the cell cycle machinery might thus be considered. This review aims at summarizing current knowledge about the role of the cell cycle machinery in post-mitotic neurons in healthy and pathological conditions.
Disciplines :
Life sciences: Multidisciplinary, general & others
Schmetsdorf S, Gärtner 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. 10.1093/cercor/bhl091 DOI: 10.1093/cercor/bhl091
Herrup K, Yang Y (2007) Cell cycle regulation in the postmitotic neuron: oxymoron or new biology? Nat Rev Neurosci 8:368–378. 10.1038/nrn2124 DOI: 10.1038/nrn2124
Yang Y, Herrup K (2007) Cell division in the CNS: protective response or lethal event in post-mitotic neurons? Biochim Biophys Acta Mol Basis Dis 1772:457–466. 10.1016/j.bbadis.2006.10.002 DOI: 10.1016/j.bbadis.2006.10.002
Frank CL, Tsai LH (2009) alternative functions of core cell cycle regulators in neuronal migration, neuronal maturation, and synaptic plasticity. Neuron 62:312–326. 10.1016/j.neuron.2009.03.029 DOI: 10.1016/j.neuron.2009.03.029
Su SC, Tsai L-H (2011) Cyclin-dependent kinases in brain development and disease. Annu Rev Cell Dev Biol 27:465–491. 10.1146/annurev-cellbio-092910-154023 DOI: 10.1146/annurev-cellbio-092910-154023
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. 10.1523/JNEUROSCI.3347-04.2004 DOI: 10.1523/JNEUROSCI.3347-04.2004
Kawauchi T, Shikanai M, Kosodo Y (2013) Extra-cell cycle regulatory functions of cyclin-dependent kinases (CDK) and CDK inhibitor proteins contribute to brain development and neurological disorders. Genes Cells Devoted Mol Cell Mech 18:176–194. 10.1111/gtc.12029 DOI: 10.1111/gtc.12029
Kawauchi T, Nabeshima Y (2019) Growth arrest triggers extra-cell cycle regulatory function in neurons: possible involvement of p27kip1 in membrane trafficking as well as cytoskeletal regulation. Front Cell Dev Biol. 10.3389/fcell.2019.00064 DOI: 10.3389/fcell.2019.00064
Iqbal N, Li Z, Chua SC (2020) Neuronal cell cycle events link caloric intake to obesity. Trends Endocrinol Metab 31:46–52. 10.1016/j.tem.2019.09.001 DOI: 10.1016/j.tem.2019.09.001
Godin JD, Nguyen L (2014) Novel functions of core cell cycle regulators in neuronal migration. In: Nguyen L, Hippenmeyer S (eds) Cellular and molecular control of neuronal migration. Springer, Dordrecht, pp 59–74
Herrup K (2013) Post-mitotic role of the cell cycle machinery. Curr Opin Cell Biol 25:711–716. 10.1016/j.ceb.2013.08.001 DOI: 10.1016/j.ceb.2013.08.001
Lolli G, Johnson LN (2005) CAK-cyclin-dependent activating kinase: a key kinase in cell cycle control and a target for drugs? Cell Cycle Georget Tex 4:572–577
Malumbres M, Barbacid M (2005) Mammalian cyclin-dependent kinases. Trends Biochem Sci 30:630–641. 10.1016/j.tibs.2005.09.005 DOI: 10.1016/j.tibs.2005.09.005
Ye X, Zhu C, Harper JW (2001) A premature-termination mutation in the Mus musculus cyclin-dependent kinase 3 gene. Proc Natl Acad Sci 98:1682–1686. 10.1073/pnas.041596198 DOI: 10.1073/pnas.041596198
Li N, Fassl A, Chick J et al (2014) Cyclin C is a haploinsufficient tumour suppressor. Nat Cell Biol 16:1080–1091. 10.1038/ncb3046 DOI: 10.1038/ncb3046
Nagano T, Hashimoto T, Nakashima A et al (2013) Cyclin I is involved in the regulation of cell cycle progression. Cell Cycle Georget Tex 12:2617–2624. 10.4161/cc.25623 DOI: 10.4161/cc.25623
Zhang J, Li H, Yabut O et al (2010) Cdk5 suppresses the neuronal cell cycle by disrupting the E2F1-DP1 complex. J Neurosci. 10.1523/JNEUROSCI.5628-09.2010 DOI: 10.1523/JNEUROSCI.5628-09.2010
Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13:1501–1512
Elledge SJ, Zhou B-BS (2000) The DNA damage response: putting checkpoints in perspective. Nature 408:433–439. 10.1038/35044005 DOI: 10.1038/35044005
Parker LL, Atherton-Fessler S, Piwnica-Worms H (1992) p107weel is a dual-specificity kinase that phosphorylates p34cdc2 on tyrosine 15 (cell cycle/baculovirus expression). Cell Biol 89:2917–2921
Lindqvist A, Rodríguez-Bravo V, Medema RH (2009) The decision to enter mitosis: feedback and redundancy in the mitotic entry network. J Cell Biol 185:20
Patil M, Pabla N, Dong Z (2013) Checkpoint kinase 1 in DNA damage response and cell cycle regulation. Cell Mol Life Sci CMLS 70:4009–4021. 10.1007/s00018-013-1307-3 DOI: 10.1007/s00018-013-1307-3
Giacinti C, Giordano A (2006) RB and cell cycle progression. Oncogene 25:5220–5227. 10.1038/sj.onc.1209615 DOI: 10.1038/sj.onc.1209615
Stevens C, La Thangue NB (2003) E2F and cell cycle control: a double-edged sword. Arch Biochem Biophys 412:157–169. 10.1016/S0003-9861(03)00054-7 DOI: 10.1016/S0003-9861(03)00054-7
Lee S-Y, Jang C, Lee K-A (2014) Polo-like kinases (plks), a key regulator of cell cycle and new potential target for cancer therapy. Dev Reprod 18:65–71. 10.12717/DR.2014.18.1.065 DOI: 10.12717/DR.2014.18.1.065
Donzelli M, Draetta GF (2003) Regulating mammalian checkpoints through Cdc25 inactivation. EMBO Rep 4:671–677. 10.1038/sj.embor.embor887 DOI: 10.1038/sj.embor.embor887
Lub S, Maes A, Maes K et al (2016) Inhibiting the anaphase promoting complex/cyclosome induces a metaphase arrest and cell death in multiple myeloma cells. Oncotarget 7:4062–4076. 10.18632/oncotarget.6768 DOI: 10.18632/oncotarget.6768
Skaar JR, Pagano M (2008) Cdh1: a master G0/G1 regulator. Nat Cell Biol 10:755–757. 10.1038/ncb0708-755 DOI: 10.1038/ncb0708-755
Cappell SD, Mark KG, Garbett D et al (2018) EMI1 switches from being a substrate to an inhibitor of APC/CCDH1 to start the cell cycle. Nature 558:313–317. 10.1038/s41586-018-0199-7 DOI: 10.1038/s41586-018-0199-7
Sumrejkanchanakij P, Tamamori-Adachi M, Matsunaga Y et al (2003) Role of cyclin D1 cytoplasmic sequestration in the survival of postmitotic neurons. Oncogene 22:8723–8730. 10.1038/sj.onc.1206870 DOI: 10.1038/sj.onc.1206870
Frade JM, Ovejero-Benito MC (2015) Neuronal cell cycle: the neuron itself and its circumstances. Cell Cycle 14:712–720. 10.1080/15384101.2015.1004937 DOI: 10.1080/15384101.2015.1004937
Odajima J, Wills ZP, Ndassa YM et al (2011) Cyclin E constrains Cdk5 activity to regulate synaptic plasticity and memory formation. Dev Cell 21:655–668. 10.1016/j.devcel.2011.08.009 DOI: 10.1016/j.devcel.2011.08.009
Itoh Y, Masuyama N, Nakayama K et al (2007) The cyclin-dependent kinase inhibitors p57 and p27 regulate neuronal migration in the developing mouse neocortex. J Biol Chem 282:390–396. 10.1074/jbc.M609944200 DOI: 10.1074/jbc.M609944200
Marín O, Valiente M, Ge X, Tsai L-H (2010) Guiding neuronal cell migrations. Cold Spring Harb Perspect Biol 2:a001834. 10.1101/cshperspect.a001834 DOI: 10.1101/cshperspect.a001834
Cicero S, Herrup K (2005) Cyclin-dependent kinase 5 is essential for neuronal cell cycle arrest and differentiation. J Neurosci 25:9658–9668. 10.1523/JNEUROSCI.1773-05.2005 DOI: 10.1523/JNEUROSCI.1773-05.2005
Li W, Allen ME, Rui Y et al (2016) p39 is responsible for increasing Cdk5 activity during postnatal neuron differentiation and governs neuronal network formation and epileptic responses. J Neurosci 36:11283–11294. 10.1523/JNEUROSCI.1155-16.2016 DOI: 10.1523/JNEUROSCI.1155-16.2016
Ohshima T, Ward JM, Huh CG et al (1996) Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Proc Natl Acad Sci USA 93:11173–11178
Ohshima T, Gilmore EC, Longenecker G et al (1999) Migration defects of cdk5(-/-) neurons in the developing cerebellum is cell autonomous. J Neurosci 19:6017–6026
Nishimura YV, Sekine K, Chihama K et al (2010) Dissecting the factors involved in the locomotion mode of neuronal migration in the developing cerebral cortex. J Biol Chem 285:5878–5887. 10.1074/jbc.M109.033761 DOI: 10.1074/jbc.M109.033761
Nishimura YV, Shikanai M, Hoshino M et al (2014) Cdk5 and its substrates, Dcx and p27kip1, regulate cytoplasmic dilation formation and nuclear elongation in migrating neurons. Dev Camb Engl 141:3540–3550. 10.1242/dev.111294 DOI: 10.1242/dev.111294
Ye T, Ip JPK, Fu AKY, Ip NY (2014) Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex. Nat Commun 5:4826. 10.1038/ncomms5826 DOI: 10.1038/ncomms5826
Tang J, Ip JPK, Ye T et al (2014) Cdk5-dependent Mst3 phosphorylation and activity regulate neuronal migration through RhoA inhibition. J Neurosci 34:7425–7436. 10.1523/JNEUROSCI.5449-13.2014 DOI: 10.1523/JNEUROSCI.5449-13.2014
Tanabe K, Yamazaki H, Inaguma Y et al (2014) Phosphorylation of drebrin by cyclin-dependent kinase 5 and its role in neuronal migration. PLoS ONE 9:e92291. 10.1371/journal.pone.0092291 DOI: 10.1371/journal.pone.0092291
Xie Z, Tsai L-H (2004) Cdk5 phosphorylation of FAK regulates centrosome-associated miocrotubules and neuronal migration. Cell Cycle Georget Tex 3:108–110
Xie Z, Sanada K, Samuels BA et al (2003) Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule organization, nuclear movement, and neuronal migration. Cell 114:469–482. 10.1016/S0092-8674(03)00605-6 DOI: 10.1016/S0092-8674(03)00605-6
Nadarajah B, Brunstrom JE, Grutzendler J et al (2001) Two modes of radial migration in early development of the cerebral cortex. Nat Neurosci 4:143–150. 10.1038/83967 DOI: 10.1038/83967
Kwon YT, Tsai LH (1998) A novel disruption of cortical development in p35(-/-) mice distinct from reeler. J Comp Neurol 395:510–522. 10.1002/(sici)1096-9861(19980615)395:4%3c510:aid-cne7%3e3.0.co;2-4 DOI: 10.1002/(sici)1096-9861(19980615)395:4%3c510::aid-cne7%3e3.0.co;2-4
Niethammer M, Smith DS, Ayala R et al (2000) NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein. Neuron 28:697–711
Sasaki S, Shionoya A, Ishida M et al (2000) A LIS1/NUDEL/cytoplasmic dynein heavy chain complex in the developing and adult nervous System. Neuron 28:681–696. 10.1016/S0896-6273(00)00146-X DOI: 10.1016/S0896-6273(00)00146-X
Cunningham JJ, Roussel MF (2001) Cyclin-dependent kinase inhibitors in the development of the central nervous system. Cell Growth Differ 12:387–396
Nguyen L, Besson A, Heng JI-T et al (2006) p27kip1 independently promotes neuronal differentiation and migration in the cerebral cortex. Genes Dev 20:1511–1524. 10.1101/gad.377106 DOI: 10.1101/gad.377106
Tury A, Mairet-Coello G, DiCicco-Bloom E (2011) The cyclin-dependent kinase inhibitor p57Kip2 regulates cell cycle exit, differentiation, and migration of embryonic cerebral cortical precursors. Cereb Cortex N Y N 1991 21:1840–1856. 10.1093/cercor/bhq254 DOI: 10.1093/cercor/bhq254
Zindy F, Cunningham JJ, Sherr CJ et al (1999) Postnatal neuronal proliferation in mice lacking Ink4d and Kip1 inhibitors of cyclin-dependent kinases. Proc Natl Acad Sci USA 96:13462–13467
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. 10.1038/ncb1338 DOI: 10.1038/ncb1338
Godin JD, Thomas N, Laguesse S et al (2012) p27Kip1 is a microtubule-associated protein that promotes microtubule polymerization during neuron migration. Dev Cell 23:729–744. 10.1016/j.devcel.2012.08.006 DOI: 10.1016/j.devcel.2012.08.006
Rodier G, Montagnoli A, Di Marcotullio L et al (2001) p27 cytoplasmic localization is regulated by phosphorylation on Ser10 and is not a prerequisite for its proteolysis. EMBO J 20:6672–6682. 10.1093/emboj/20.23.6672 DOI: 10.1093/emboj/20.23.6672
Kotake Y, Nakayama K, Ishida N, Nakayama KI (2005) Role of serine 10 phosphorylation in p27 stabilization revealed by analysis of p27 knock-in mice harboring a serine 10 mutation. J Biol Chem 280:1095–1102. 10.1074/jbc.M406117200 DOI: 10.1074/jbc.M406117200
Clément O, Hemming IA, Gladwyn-Ng IE et al (2017) Rp58 and p27(kip1) coordinate cell cycle exit and neuronal migration within the embryonic mouse cerebral cortex. Neural Dev 12:8. 10.1186/s13064-017-0084-3 DOI: 10.1186/s13064-017-0084-3
Kranenburg O, Scharnhorst V, Van der Eb AJ, Zantema A (1995) Inhibition of cyclin-dependent kinase activity triggers neuronal differentiation of mouse neuroblastoma cells. J Cell Biol 131:227–234
Ferguson KL, Vanderluit JL, Hébert JM et al (2002) Telencephalon-specific Rb knockouts reveal enhanced neurogenesis, survival and abnormal cortical development. EMBO J 21:3337–3346. 10.1093/emboj/cdf338 DOI: 10.1093/emboj/cdf338
Ferguson KL, McClellan KA, Vanderluit JL et al (2005) A cell-autonomous requirement for the cell cycle regulatory protein, Rb, in neuronal migration. EMBO J 24:4381–4391. 10.1038/sj.emboj.7600887 DOI: 10.1038/sj.emboj.7600887
Svoboda DS, Paquin A, Park DS, Slack RS (2013) Pocket proteins pRb and p107 are required for cortical lamination independent of apoptosis. Dev Biol 384:101–113. 10.1016/j.ydbio.2013.09.015 DOI: 10.1016/j.ydbio.2013.09.015
McClellan KA, Ruzhynsky VA, Douda DN et al (2007) Unique requirement for Rb/E2F3 in neuronal migration: evidence for cell cycle-independent functions. Mol Cell Biol 27:4825–4843. 10.1128/MCB.02100-06 DOI: 10.1128/MCB.02100-06
Eguren M, Manchado E, Malumbres M (2011) Non-mitotic functions of the anaphase-promoting complex. Semin Cell Dev Biol 22:572–578
Delgado-Esteban M, García-Higuera I, Maestre C et al (2013) APC/C-Cdh1 coordinates neurogenesis and cortical size during development. Nat Commun 4:2879. 10.1038/ncomms3879 DOI: 10.1038/ncomms3879
Draghetti C, Salvat C, Zanoguera F et al (2009) Functional whole-genome analysis identifies polo-like kinase 2 and poliovirus receptor as essential for neuronal differentiation upstream of the negative regulator? B-crystallin. J Biol Chem 284:32053–32065. 10.1074/jbc.M109.009324 DOI: 10.1074/jbc.M109.009324
Schmetsdorf S, Arnold E, Holzer M et al (2009) A putative role for cell cycle-related proteins in microtubule-based neuroplasticity. Eur J Neurosci 29:1096–1107. 10.1111/j.1460-9568.2009.06661.x DOI: 10.1111/j.1460-9568.2009.06661.x
Mandelkow E-M, Stamer K, Vogel R et al (2003) Clogging of axons by tau, inhibition of axonal traffic and starvation of synapses. Neurobiol Aging 24:1079–1085. 10.1016/j.neurobiolaging.2003.04.007 DOI: 10.1016/j.neurobiolaging.2003.04.007
Nikolic M, Dudek H, Kwon YT et al (1996) The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation. Genes Dev 10:816–825. 10.1101/gad.10.7.816 DOI: 10.1101/gad.10.7.816
Piccini A, Perlini LE, Cancedda L et al (2015) Phosphorylation by PKA and Cdk5 mediates the early effects of synapsin III in neuronal morphological maturation. J Neurosci 35:13148–13159. 10.1523/JNEUROSCI.1379-15.2015 DOI: 10.1523/JNEUROSCI.1379-15.2015
Furusawa K, Asada A, Urrutia P et al (2017) Cdk5 Regulation of the GRAB-mediated Rab8-Rab11 cascade in axon outgrowth. J Neurosci 37:790–806. 10.1523/JNEUROSCI.2197-16.2016 DOI: 10.1523/JNEUROSCI.2197-16.2016
Shah K, Rossie S (2018) Tale of the good and the bad Cdk5: remodeling of the actin cytoskeleton in the brain. Mol Neurobiol 55:3426–3438. 10.1007/s12035-017-0525-3 DOI: 10.1007/s12035-017-0525-3
Huang H, Lin X, Liang Z et al (2017) Cdk5-dependent phosphorylation of liprinα1 mediates neuronal activity-dependent synapse development. Proc Natl Acad Sci USA 114:E6992–E7001. 10.1073/pnas.1708240114 DOI: 10.1073/pnas.1708240114
Morabito MA (2004) Cyclin-dependent kinase 5 phosphorylates the N-terminal domain of the postsynaptic density protein PSD-95 in neurons. J Neurosci 24:865–876. 10.1523/JNEUROSCI.4582-03.2004 DOI: 10.1523/JNEUROSCI.4582-03.2004
Cheung ZH, Fu AKY, Ip NY (2006) Synaptic roles of Cdk5: implications in higher cognitive functions and neurodegenerative diseases. Neuron 50:13–18. 10.1016/J.NEURON.2006.02.024 DOI: 10.1016/J.NEURON.2006.02.024
Cheng K, Ip NY (2003) Cdk5: a new player at synapses. Neurosignals 12:180–190. 10.1159/000074619 DOI: 10.1159/000074619
Fletcher AI, Shuang R, Giovannucci DR et al (1999) Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of Munc18. J Biol Chem 274:4027–4035. 10.1074/jbc.274.7.4027 DOI: 10.1074/jbc.274.7.4027
Tan TC, Valova VA, Malladi CS et al (2003) Cdk5 is essential for synaptic vesicle endocytosis. Nat Cell Biol 5:701–710. 10.1038/ncb1020 DOI: 10.1038/ncb1020
Tomizawa K, Sunada S, Lu Y-F et al (2003) Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles. J Cell Biol 163:813–824. 10.1083/jcb.200308110 DOI: 10.1083/jcb.200308110
Nguyen C, Bibb JA (2003) Cdk5 and the mystery of synaptic vesicle endocytosis. J Cell Biol 163:697–699. 10.1083/jcb.200310038 DOI: 10.1083/jcb.200310038
Seeburg DP, Feliu-Mojer M, Gaiottino J et al (2008) Critical role of CDK5 and Polo-like kinase 2 in homeostatic synaptic plasticity during elevated activity. Neuron 58:571–583. 10.1016/j.neuron.2008.03.021 DOI: 10.1016/j.neuron.2008.03.021
Fu AKY, Fu W-Y, Cheung J et al (2001) Cdk5 is involved in neuregulin-induced AChR expression at the neuromuscular junction. Nat Neurosci 4:374–381. 10.1038/86019 DOI: 10.1038/86019
Bibb JA (2003) Role of Cdk5 in neuronal signaling, plasticity, and drug abuse. Neurosignals 12:191–199. 10.1159/000074620 DOI: 10.1159/000074620
Moy LY, Tsai L-H (2004) Cyclin-dependent kinase 5 phosphorylates serine 31 of tyrosine hydroxylase and regulates its stability. J Biol Chem 279:54487–54493. 10.1074/jbc.M406636200 DOI: 10.1074/jbc.M406636200
Posada-Duque RA, Ramirez O, Härtel S et al (2017) CDK5 downregulation enhances synaptic plasticity. Cell Mol Life Sci CMLS 74:153–172. 10.1007/s00018-016-2333-8 DOI: 10.1007/s00018-016-2333-8
Hernandez A, Tan C, Mettlach G et al (2016) Cdk5 modulates long-term synaptic plasticity and motor learning in dorsolateral striatum. Sci Rep 6:29812. 10.1038/srep29812 DOI: 10.1038/srep29812
Ghose A, Shashidhara LS (2011) Cyclin beyond the cell cycle: new partners at the synapse. Dev Cell 21:601–602. 10.1016/j.devcel.2011.09.015 DOI: 10.1016/j.devcel.2011.09.015
Cho E, Kim D-H, Hur Y-N et al (2015) Cyclin Y inhibits plasticity-induced AMPA receptor exocytosis and LTP. Sci Rep 5:12624. 10.1038/srep12624 DOI: 10.1038/srep12624
He G, Yang X, Wang G et al (2017) Cdk7 is required for activity-dependent neuronal gene expression, long-lasting synaptic plasticity and long-term memory. Front Mol Neurosci 10:365. 10.3389/fnmol.2017.00365 DOI: 10.3389/fnmol.2017.00365
Morelli G, Even A, Gladwyn-Ng I et al (2018) p27Kip1 modulates axonal transport by regulating α-tubulin acetyltransferase 1 stability. Cell Rep 23:2429–2442. 10.1016/j.celrep.2018.04.083 DOI: 10.1016/j.celrep.2018.04.083
Ting JH, Marks DR, Schleidt SS et al (2014) Targeted gene mutation of E2F1 evokes age-dependent synaptic disruption and behavioral deficits. J Neurochem 129:850–863. 10.1111/jnc.12655 DOI: 10.1111/jnc.12655
Konishi Y, Stegmüller J, Matsuda T et al (2004) Cdh1-APC controls axonal growth and patterning in the mammalian brain. Science 303:1026–1030. 10.1126/science.1093712 DOI: 10.1126/science.1093712
Lasorella A, Stegmüller J, Guardavaccaro D et al (2006) Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth. Nature 442:471–474. 10.1038/nature04895 DOI: 10.1038/nature04895
Stegmüller J, Konishi Y, Huynh MA et al (2006) Cell-intrinsic regulation of axonal morphogenesis by the Cdh1-APC target SnoN. Neuron 50:389–400. 10.1016/j.neuron.2006.03.034 DOI: 10.1016/j.neuron.2006.03.034
van Roessel P, Elliott DA, Robinson IM et al (2004) Independent regulation of synaptic size and activity by the anaphase-promoting complex. Cell 119:707–718. 10.1016/j.cell.2004.11.028 DOI: 10.1016/j.cell.2004.11.028
Kim AH, Puram SV, Bilimoria PM et al (2009) A centrosomal Cdc20-APC pathway controls dendrite morphogenesis in postmitotic neurons. Cell 136:322–336. 10.1016/j.cell.2008.11.050 DOI: 10.1016/j.cell.2008.11.050
Yang Y, Kim AH, Yamada T et al (2009) A Cdc20-APC ubiquitin signaling pathway regulates presynaptic differentiation. Science 326:575–578. 10.1126/science.1177087 DOI: 10.1126/science.1177087
Fishel ML, Vasko MR, Kelley MR (2007) DNA repair in neurons: so if they don’t divide what’s to repair? Mutat Res Mol Mech Mutagen 614:24–36. 10.1016/j.mrfmmm.2006.06.007 DOI: 10.1016/j.mrfmmm.2006.06.007
Nouspikel T, Hanawalt PC (2002) DNA repair in terminally differentiated cells. DNA Repair 1:59–75
Uttara B, Singh AV, Zamboni P, Mahajan RT (2009) Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 7:65–74. 10.2174/157015909787602823 DOI: 10.2174/157015909787602823
Narciso L, Parlanti E, Racaniello M et al (2016) The response to oxidative DNA damage in neurons: mechanisms and disease. Neural Plast 2016:1–14. 10.1155/2016/3619274 DOI: 10.1155/2016/3619274
Welty S, Teng Y, Liang Z et al (2018) RAD52 is required for RNA-templated recombination repair in post-mitotic neurons. J Biol Chem 293:1353–1362. 10.1074/jbc.M117.808402 DOI: 10.1074/jbc.M117.808402
Tomashevski A, Webster DR, Grammas P et al (2010) Cyclin-C-dependent cell-cycle entry is required for activation of non-homologous end joining DNA repair in postmitotic neurons. Cell Death Differ 17:1189–1198. 10.1038/cdd.2009.221 DOI: 10.1038/cdd.2009.221
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. 10.1038/ncb1829 DOI: 10.1038/ncb1829
Schwartz EI, Smilenov LB, Price MA et al (2007) Cell cycle activation in postmitotic neurons is essential for DNA repair. Cell Cycle Georget Tex 6:318–329. 10.4161/cc.6.3.3752 DOI: 10.4161/cc.6.3.3752
Casafont I, Palanca A, Lafarga V et al (2011) Effect of ionizing radiation in sensory ganglion neurons: organization and dynamics of nuclear compartments of DNA damage/repair and their relationship with transcription and cell cycle. Acta Neuropathol (Berl) 122:481–493. 10.1007/s00401-011-0869-0 DOI: 10.1007/s00401-011-0869-0
Biswas SC, Zhang Y, Iyirhiaro G et al (2010) Sertad1 plays an essential role in developmental and pathological neuron death. J Neurosci 30:3973–3982. 10.1523/JNEUROSCI.6421-09.2010 DOI: 10.1523/JNEUROSCI.6421-09.2010
Wen Y, Yang S, Liu R, Simpkins JW (2005) Cell-cycle regulators are involved in transient cerebral ischemia induced neuronal apoptosis in female rats. FEBS Lett 579:4591–4599. 10.1016/j.febslet.2005.07.028 DOI: 10.1016/j.febslet.2005.07.028
Marlier Q, Jibassia F, Verteneuil S et al (2018) Genetic and pharmacological inhibition of Cdk1 provides neuroprotection towards ischemic neuronal death. Cell death Discover. 10.1038/s41420-018-0044-7 DOI: 10.1038/s41420-018-0044-7
Kruman II, Wersto RP, Cardozo-Pelaez F et al (2004) Cell cycle activation linked to neuronal cell death initiated by DNA damage. Neuron 41:549–561
Park DS, Levine B, Ferrari G, Greene LA (1997) 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
Park DS, Morris EJ, Padmanabhan J et al (1998) Cyclin-dependent kinases participate in death of neurons evoked by DNA-damaging agents. J Cell Biol 143:457–467. 10.1083/jcb.143.2.457 DOI: 10.1083/jcb.143.2.457
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
Park DS, Morris EJ, Bremner R et al (2000) Involvement of retinoblastoma family members and E2F/DP complexes in the death of neurons evoked by DNA damage. J Neurosci 20:3104–3114
Lin WC, Lin FT, Nevins JR (2001) Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation. Genes Dev 15:1833–1844
Hershko T, Ginsberg D (2004) Up-regulation of Bcl-2 Homology 3 (BH3)-only Proteins by E2F1 Mediates Apoptosis. J Biol Chem 279:8627–8634. 10.1074/jbc.M312866200 DOI: 10.1074/jbc.M312866200
Stanelle J, Stiewe T, Theseling CC et al (2002) Gene expression changes in response to E2F1 activation. Nucleic Acids Res 30:1859–1859
Hsieh J-K, Yap D, O’Connor DJ et al (2002) Novel function of the cyclin A binding site of E2F in regulating p53-induced apoptosis in response to DNA damage. Mol Cell Biol 22:78–93. 10.1128/MCB.22.1.78-93.2002 DOI: 10.1128/MCB.22.1.78-93.2002
Hou ST, Cowan E, Walker T et al (2001) The transcription factor E2F1 promotes dopamine-evoked neuronal apoptosis by a mechanism independent of transcriptional activation. J Neurochem 78:287–297
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
Wu J, Sabirzhanov B, Stoica BA et al (2015) Ablation of the transcription factors E2F1-2 limits neuroinflammation and associated neurological deficits after contusive spinal cord injury. Cell Cycle Georget Tex 14:3698–3712. 10.1080/15384101.2015.1104436 DOI: 10.1080/15384101.2015.1104436
Copani A, Condorelli F, Caruso A et al (1999) Mitotic signaling by beta-amyloid causes neuronal death. FASEB J 13:2225–2234
Kuan C-Y (2004) Hypoxia-ischemia induces DNA synthesis without cell proliferation in dying neurons in adult rodent brain. J Neurosci 24:10763–10772. 10.1523/JNEUROSCI.3883-04.2004 DOI: 10.1523/JNEUROSCI.3883-04.2004
Smith DS, Leone G, DeGregori J et al (2000) Induction of DNA replication in adult rat neurons by deregulation of the retinoblastoma/E2F G1 cell cycle pathway. Cell Growth Differ Mol Biol J Am Assoc Cancer Res 11:625–633
Verdaguer E, García-Jordà E, Canudas AM et al (2002) Kainic acid-induced apoptosis in cerebellar granule neurons: an attempt at cell cycle re-entry. NeuroReport 13:413–416
Veas-Pérez de Tudela M, Delgado-Esteban M, Maestre C et al (2015) Regulation of Bcl-xL-ATP synthase interaction by mitochondrial cyclin B1-cyclin-dependent kinase-1 determines neuronal survival. J Neurosci 35:9287–9301. 10.1523/JNEUROSCI.4712-14.2015 DOI: 10.1523/JNEUROSCI.4712-14.2015
Yuan Z, Becker EBE, Merlo P et al (2008) Activation of FOXO1 by Cdk1 in cycling cells and postmitotic neurons. Science 319:1665–1668. 10.1126/science.1152337 DOI: 10.1126/science.1152337
Lee MS, Kwon YT, Li M et al (2000) Neurotoxicity induces cleavage of p35 to p25 by calpain. Nature 405:360–364. 10.1038/35012636 DOI: 10.1038/35012636
Zhang J, Krishnamurthy PK, Johnson GVW (2002) Cdk5 phosphorylates p53 and regulates its activity. J Neurochem 81:307–313
Guo D, Xie W, Xiong P et al (2018) Cyclin-dependent kinase 5-mediated phosphorylation of chloride intracellular channel 4 promotes oxidative stress-induced neuronal death. Cell Death Dis 9:951. 10.1038/s41419-018-0983-1 DOI: 10.1038/s41419-018-0983-1
Veas-Pérez de Tudela M, Maestre C, Delgado-Esteban M et al (2015) Cdk5-mediated inhibition of APC/C-Cdh1 switches on the cyclin D1-Cdk4-pRb pathway causing aberrant S-phase entry of postmitotic neurons. Sci Rep 5:18180. 10.1038/srep18180 DOI: 10.1038/srep18180
Hamdane M, Bretteville A, Sambo A-V et al (2005) p25/Cdk5-mediated retinoblastoma phosphorylation is an early event in neuronal cell death. J Cell Sci 118:1291–1298. 10.1242/jcs.01724 DOI: 10.1242/jcs.01724
Chang K-H, Vincent F, Shah K (2012) Deregulated Cdk5 triggers aberrant activation of cell cycle kinases and phosphatases inducing neuronal death. J Cell Sci 125:5124–5137. 10.1242/jcs.108183 DOI: 10.1242/jcs.108183
Jurk D, Wang C, Miwa S et al (2012) Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response. Aging Cell 11:996–1004. 10.1111/j.1474-9726.2012.00870.x DOI: 10.1111/j.1474-9726.2012.00870.x
Wan C, Liu J, Nie X et al (2014) 2, 3, 7, 8-Tetrachlorodibenzo-P-dioxin (TCDD) induces premature senescence in human and rodent neuronal cells via ROS-dependent mechanisms. PLoS ONE 9:e89811. 10.1371/journal.pone.0089811 DOI: 10.1371/journal.pone.0089811
Martínez-Cué C, Rueda N (2020) Cellular senescence in neurodegenerative diseases. Front Cell Neurosci. 10.3389/fncel.2020.00016 DOI: 10.3389/fncel.2020.00016
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 (Berl) 93:294–300
Smith TW, Lippa CF (1995) Ki-67 immunoreactivity in Alzheimer’s disease and other neurodegenerative disorders. J Neuropathol Exp Neurol 54:297–303
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. 10.1523/JNEUROSCI.3707-05.2006 DOI: 10.1523/JNEUROSCI.3707-05.2006
Esteras N, Bartolomé F, Alquézar C et al (2012) Altered cell cycle-related gene expression in brain and lymphocytes from a transgenic mouse model of Alzheimer’s disease [amyloid precursor protein/presenilin 1 (PS1)]. Eur J Neurosci 36:2609–2618. 10.1111/j.1460-9568.2012.08178.x DOI: 10.1111/j.1460-9568.2012.08178.x
Ogawa O, Zhu X, Lee H-G et al (2003) Ectopic localization of phosphorylated histone H3 in Alzheimer’s disease: a mitotic catastrophe? Acta Neuropathol (Berl) 105:524–528. 10.1007/s00401-003-0684-3 DOI: 10.1007/s00401-003-0684-3
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
Pei J-J, Braak H, Gong C-X et al (2002) Up-regulation of cell division cycle (cdc) 2 kinase in neurons with early stage Alzheimer’s disease neurofibrillary degeneration. Acta Neuropathol (Berl) 104:369–376. 10.1007/s00401-002-0565-1 DOI: 10.1007/s00401-002-0565-1
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
Jordan-Sciutto KL, Malaiyandi LM, Bowser R (2002) Altered distribution of cell cycle transcriptional regulators during Alzheimer disease. J Neuropathol Exp Neurol 61:20
Huang F, Wang M, Liu R et al (2018) CDT2-controlled cell cycle reentry regulates the pathogenesis of Alzheimer’s disease. Alzheimers Dement J Alzheimers Assoc. 10.1016/j.jalz.2018.08.013 DOI: 10.1016/j.jalz.2018.08.013
López-Sánchez N, Fontán-Lozano Á, Pallé A et al (2017) Neuronal tetraploidization in the cerebral cortex correlates with reduced cognition in mice and precedes and recapitulates Alzheimer’s-associated neuropathology. Neurobiol Aging 56:50–66. 10.1016/j.neurobiolaging.2017.04.008 DOI: 10.1016/j.neurobiolaging.2017.04.008
Yang Y, Geldmacher DS, Herrup K et al (2001) DNA replication precedes neuronal cell death in Alzheimer’s disease. J Neurosci 21:2661–2668
Zhu X, Siedlak SL, Wang Y et al (2008) Neuronal binucleation in Alzheimer disease hippocampus. Neuropathol Appl Neurobiol 34:457–465. 10.1111/j.1365-2990.2007.00908.x DOI: 10.1111/j.1365-2990.2007.00908.x
Spremo-Potparević B, Živković L, Djelić N et al (2008) Premature centromere division of the X chromosome in neurons in Alzheimer’s disease. J Neurochem 106:2218–2223. 10.1111/j.1471-4159.2008.05555.x DOI: 10.1111/j.1471-4159.2008.05555.x
Barrio-Alonso E, Hernández-Vivanco A, Walton CC et al (2018) Cell cycle reentry triggers hyperploidization and synaptic dysfunction followed by delayed cell death in differentiated cortical neurons. Sci Rep 8:14316. 10.1038/s41598-018-32708-4 DOI: 10.1038/s41598-018-32708-4
Arendt T, Rödel L, Gärtner U, Holzer M (1996) Expression of the cyclin-dependent kinase inhibitor p16 in Alzheimer’s disease. NeuroReport 7:3047–3049
McShea A, Harris PL, Webster KR et al (1997) Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer’s disease. Am J Pathol 150:1933–1939
Lee KY, Clark AW, Rosales JL et al (1999) Elevated neuronal Cdc2-like kinase activity in the Alzheimer disease brain. Neurosci Res 34:21–29
Kimura T, Ishiguro K, Hisanaga S-I (2014) Physiological and pathological phosphorylation of tau by Cdk5. Front Mol Neurosci 7:65. 10.3389/fnmol.2014.00065 DOI: 10.3389/fnmol.2014.00065
Patrick GN, Zukerberg L, Nikolic M et al (1999) Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature 402:615–622. 10.1038/45159 DOI: 10.1038/45159
Wada Y, Ishiguro K, Itoh TJ et al (1998) Microtubule-stimulated phosphorylation of tau at Ser202 and Thr205 by cdk5 decreases its microtubule nucleation activity. J Biochem (Tokyo) 124:738–746. 10.1093/oxfordjournals.jbchem.a022174 DOI: 10.1093/oxfordjournals.jbchem.a022174
Liu F, Su Y, Li B et al (2003) Regulation of amyloid precursor protein (APP) phosphorylation and processing by p35/Cdk5 and p25/Cdk5. FEBS Lett 547:193–196
Cruz JC, Tsai L-H (2004) Cdk5 deregulation in the pathogenesis of Alzheimer’s disease. Trends Mol Med 10:452–458. 10.1016/j.molmed.2004.07.001 DOI: 10.1016/j.molmed.2004.07.001
Shukla V, Skuntz S, Pant HC (2012) Deregulated Cdk5 activity is involved in inducing Alzheimer’s disease. Arch Med Res 43:655–662. 10.1016/j.arcmed.2012.10.015 DOI: 10.1016/j.arcmed.2012.10.015
Wilkaniec A, Czapski GA, Adamczyk A (2016) Cdk5 at crossroads of protein oligomerization in neurodegenerative diseases: facts and hypotheses. J Neurochem 136:222–233. 10.1111/jnc.13365 DOI: 10.1111/jnc.13365
Jaiswal S, Sharma P (2017) Role and regulation of p27 in neuronal apoptosis. J Neurochem 140:576–588. 10.1111/jnc.13918 DOI: 10.1111/jnc.13918
Lapresa R, Agulla J, Sánchez-Morán I et al (2018) Amyloid-ß promotes neurotoxicity by Cdk5-induced p53 stabilization. Neuropharmacology 146:19–27. 10.1016/j.neuropharm.2018.11.019 DOI: 10.1016/j.neuropharm.2018.11.019
Shi C, Viccaro K, Lee H-G, Shah K (2016) Cdk5-Foxo3 axis: initially neuroprotective, eventually neurodegenerative in Alzheimer’s disease models. J Cell Sci 129:1815–1830. 10.1242/jcs.185009 DOI: 10.1242/jcs.185009
Alvarez A, Toro R, Cáceres A, Maccioni RB (1999) Inhibition of tau phosphorylating protein kinase cdk5 prevents β-amyloid-induced neuronal death. FEBS Lett 459:421–426. 10.1016/S0014-5793(99)01279-X DOI: 10.1016/S0014-5793(99)01279-X
Lopes JP, Oliveira CR, Agostinho P (2009) Cdk5 acts as a mediator of neuronal cell cycle re-entry triggered by amyloid-β and prion peptides. Cell Cycle 8:97–104
Piedrahita D, Hernández I, López-Tobón A et al (2010) Silencing of CDK5 reduces neurofibrillary tangles in transgenic alzheimer’s mice. J Neurosci 30:13966–13976. 10.1523/JNEUROSCI.3637-10.2010 DOI: 10.1523/JNEUROSCI.3637-10.2010
Zheng Y-L, Amin ND, Hu Y-F et al (2010) A 24-residue peptide (p5), derived from p35, the Cdk5 neuronal activator, specifically inhibits Cdk5-p25 hyperactivity and tau hyperphosphorylation. J Biol Chem 285:34202–34212. 10.1074/jbc.M110.134643 DOI: 10.1074/jbc.M110.134643
Zheng Y, Li B-S, Amin ND et al (2002) A peptide derived from cyclin-dependent kinase activator (p35) specifically inhibits Cdk5 activity and phosphorylation of tau protein in transfected cells. Eur J Biochem 269:4427–4434. 10.1046/j.1432-1033.2002.03133.x DOI: 10.1046/j.1432-1033.2002.03133.x
Zheng Y-L, Kesavapany S, Gravell M et al (2005) A Cdk5 inhibitory peptide reduces tau hyperphosphorylation and apoptosis in neurons. EMBO J 24:209–220. 10.1038/sj.emboj.7600441 DOI: 10.1038/sj.emboj.7600441
Sundaram JR, Poore CP, Sulaimee NHB et al (2013) Specific inhibition of p25/Cdk5 activity by the Cdk5 inhibitory peptide reduces neurodegeneration in vivo. J Neurosci 33:334–343. 10.1523/JNEUROSCI.3593-12.2013 DOI: 10.1523/JNEUROSCI.3593-12.2013
Bk B, Skuntz S, Prochazkova M et al (2019) Overexpression of the Cdk5 inhibitory peptide in motor neurons rescue of amyotrophic lateral sclerosis phenotype in a mouse model. Hum Mol Genet 28:3175–3187. 10.1093/hmg/ddz118 DOI: 10.1093/hmg/ddz118
Bergeron M, Motter R, Tanaka P et al (2014) In vivo modulation of polo-like kinases supports a key role for PLK2 in Ser129 α-synuclein phosphorylation in mouse brain. Neuroscience 256:72–82. 10.1016/j.neuroscience.2013.09.061 DOI: 10.1016/j.neuroscience.2013.09.061
Inglis KJ, Chereau D, Brigham EF et al (2009) Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system. J Biol Chem 284:2598–2602. 10.1074/jbc.C800206200 DOI: 10.1074/jbc.C800206200
Alvira D, Tajes M, Verdaguer E et al (2007) Inhibition of cyclin-dependent kinases is neuroprotective in 1-methyl-4-phenylpyridinium-induced apoptosis in neurons. Neuroscience 146:350–365. 10.1016/j.neuroscience.2007.01.042 DOI: 10.1016/j.neuroscience.2007.01.042
El-Khodor BF, Oo TF, Kholodilov N, Burke RE (2003) Ectopic expression of cell cycle markers in models of induced programmed cell death in dopamine neurons of the rat substantia nigra pars compacta. Exp Neurol 179:17–27
Höglinger GU, Breunig JJ, Depboylu C et al (2007) The pRb/E2F cell-cycle pathway mediates cell death in Parkinson’s disease. Proc Natl Acad Sci U S A 104:3585–3590. 10.1073/pnas.0611671104 DOI: 10.1073/pnas.0611671104
Jordan-Sciutto KL, Dorsey R, Chalovich EM et al (2003) Expression patterns of retinoblastoma protein in Parkinson disease. J Neuropathol Exp Neurol 62:68–74
Smith PD, O’Hare MJ, Park DS (2004) CDKs: taking on a role as mediators of dopaminergic loss in Parkinson’s disease. Trends Mol Med 10:445–451. 10.1016/j.molmed.2004.07.003 DOI: 10.1016/j.molmed.2004.07.003
Gallastegui E, Domuro C, Serratosa J et al (2018) p27Kip1 regulates alpha-synuclein expression. Oncotarget 9:16368–16379. 10.18632/oncotarget.24687 DOI: 10.18632/oncotarget.24687
Alvira D, Ferrer I, Gutierrez-Cuesta J et al (2008) Activation of the calpain/cdk5/p25 pathway in the girus cinguli in Parkinson’s disease. Parkinsonism Relat Disord 14:309–313. 10.1016/j.parkreldis.2007.09.005 DOI: 10.1016/j.parkreldis.2007.09.005
Smith PD, Crocker SJ, Jackson-Lewis V et al (2003) Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson’s disease. Proc Natl Acad Sci USA 100:13650–13655. 10.1073/pnas.2232515100 DOI: 10.1073/pnas.2232515100
Crocker SJ, Smith PD, Jackson-Lewis V et al (2003) Inhibition of calpains prevents neuronal and behavioral deficits in an MPTP mouse model of Parkinson’s disease. J Neurosci 23:4081–4091
Wen Z, Shu Y, Gao C et al (2014) CDK5-mediated phosphorylation and autophagy of RKIP regulate neuronal death in Parkinson’s disease. Neurobiol Aging 35:2870–2880. 10.1016/j.neurobiolaging.2014.05.034 DOI: 10.1016/j.neurobiolaging.2014.05.034
Qu D, Rashidian J, Mount MP et al (2007) Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson’s disease. Neuron 55:37–52. 10.1016/j.neuron.2007.05.033 DOI: 10.1016/j.neuron.2007.05.033
Smith PD, Mount MP, Shree R et al (2006) Calpain-regulated p35/cdk5 plays a central role in dopaminergic neuron death through modulation of the transcription factor myocyte enhancer factor 2. J Neurosci 26:440–447. 10.1523/JNEUROSCI.2875-05.2006 DOI: 10.1523/JNEUROSCI.2875-05.2006
Binukumar BK, Shukla V, Amin ND et al (2015) Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson’s disease. Mol Biol Cell 26:4478–4491. 10.1091/mbc.E15-06-0415 DOI: 10.1091/mbc.E15-06-0415
He R, Huang W, Huang Y et al (2018) Cdk5 inhibitory peptide prevents loss of dopaminergic neurons and alleviates behavioral changes in an MPTP induced Parkinson’s disease mouse model. Front Aging Neurosci 10:162. 10.3389/fnagi.2018.00162 DOI: 10.3389/fnagi.2018.00162
Zhang Q, Xie H, Ji Z et al (2016) Cdk5/p25 specific inhibitory peptide TFP5 rescues the loss of dopaminergic neurons in a sub-acute MPTP induced PD mouse model. Neurosci Lett 632:1–7. 10.1016/j.neulet.2016.08.023 DOI: 10.1016/j.neulet.2016.08.023
Rashidian J, Iyirhiaro G, Aleyasin H et al (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. 10.1073/pnas.0500099102 DOI: 10.1073/pnas.0500099102
Chen B, Wang W (2008) The expression of Cyclins in neurons of rats after focal cerebral ischemia. J Huazhong Univ Sci Technol Med Sci 28:60–64. 10.1007/s11596-008-0115-8 DOI: 10.1007/s11596-008-0115-8
Katchanov J, Harms C, Gertz K et al (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
Iyirhiaro GO, Im DS, Boonying W et al (2017) Cdc25A is a critical mediator of ischemic neuronal death in vitro and in vivo. J Neurosci. 10.1523/JNEUROSCI.3017-16.2017 DOI: 10.1523/JNEUROSCI.3017-16.2017
Schmidt-Kastner R, Truettner J, Zhao W et al (2000) Differential changes of bax, caspase-3 and p21 mRNA expression after transient focal brain ischemia in the rat. Brain Res Mol Brain Res 79:88–101
Gendron TF, Mealing GA, Paris J et al (2001) Attenuation of neurotoxicity in cortical cultures and hippocampal slices from E2F1 knockout mice. J Neurochem 78:316–324
Meyer DA, Torres-Altoro MI, Tan Z et al (2014) Ischemic stroke injury is mediated by aberrant Cdk5. J Neurosci 34:8259–8267. 10.1523/JNEUROSCI.4368-13.2014 DOI: 10.1523/JNEUROSCI.4368-13.2014
Menn B, Bach S, Blevins TL et al (2010) Delayed treatment with systemic (s)-roscovitine provides neuroprotection and inhibits in vivo CDK5 activity increase in animal stroke models. PLoS ONE 5:e12117. 10.1371/journal.pone.0012117 DOI: 10.1371/journal.pone.0012117
Wang J, Liu S, Fu Y et al (2003) Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors. Nat Neurosci Publ 6:1039. 10.1038/NN1119 DOI: 10.1038/NN1119
Liu S-L, Wang C, Jiang T et al (2016) The role of Cdk5 in Alzheimer’s disease. Mol Neurobiol 53:4328–4342. 10.1007/s12035-015-9369-x DOI: 10.1007/s12035-015-9369-x
Shah K, Lahiri DK (2014) Cdk5 activity in the brain—multiple paths of regulation. J Cell Sci 127:2391–2400. 10.1242/jcs.147553 DOI: 10.1242/jcs.147553
Slevin M, Krupinski J (2009) Cyclin-dependent kinase-5 targeting for ischaemic stroke. Curr Opin Pharmacol 9:119–124
Mitsios N, Pennucci R, Krupinski J et al (2007) Expression of cyclin-dependent kinase 5 mRNA and protein in the human brain following acute ischemic stroke. Brain Pathol Zurich Switz 17:11–23. 10.1111/j.1750-3639.2006.00031.x DOI: 10.1111/j.1750-3639.2006.00031.x
Dumont RJ, Okonkwo DO, Verma S et al (2001) Acute spinal cord injury, part I: pathophysiologic mechanisms. Clin Neuropharmacol 24:254–264. 10.1097/00002826-200109000-00002 DOI: 10.1097/00002826-200109000-00002
Stoica BA, Faden AI (2010) Cell death mechanisms and modulation in traumatic brain injury. Neurotherapeutics 7:3–12. 10.1016/j.nurt.2009.10.023 DOI: 10.1016/j.nurt.2009.10.023
Byrnes KR, Stoica BA, Fricke S et al (2007) Cell cycle activation contributes to post-mitotic cell death and secondary damage after spinal cord injury. Brain 130:2977–2992. 10.1093/brain/awm179 DOI: 10.1093/brain/awm179
Di Giovanni S, Knoblach SM, Brandoli C et al (2003) Gene profiling in spinal cord injury shows role of cell cycle in neuronal death. Ann Neurol 53:454–468. 10.1002/ana.10472 DOI: 10.1002/ana.10472
Kabadi SV, Stoica BA, Loane DJ et al (2014) CR8, a novel inhibitor of CDK, limits microglial activation, astrocytosis, neuronal loss, and neurologic dysfunction after experimental traumatic brain injury. J Cereb Blood Flow Metab 34:502–513. 10.1038/jcbfm.2013.228 DOI: 10.1038/jcbfm.2013.228
Sakurai M, Hayashi T, Abe K et al (2000) Cyclin D1 and Cdk4 protein induction in motor neurons after transient spinal cord ischemia in rabbits. Stroke J Cereb Circ 31:200–207
Skovira JW, Wu J, Matyas JJ et al (2016) Cell cycle inhibition reduces inflammatory responses, neuronal loss, and cognitive deficits induced by hypobaria exposure following traumatic brain injury. J Neuroinflammation 13:299. 10.1186/s12974-016-0769-2 DOI: 10.1186/s12974-016-0769-2
Aubrecht TG, Faden AI, Sabirzhanov B et al (2018) Comparing effects of CDK inhibition and E2F1/2 ablation on neuronal cell death pathways in vitro and after traumatic brain injury. Cell Death Dis. 10.1038/s41419-018-1156-y DOI: 10.1038/s41419-018-1156-y
Stone JG, Siedlak SL, Tabaton M et al (2011) The cell cycle regulator phosphorylated retinoblastoma protein is associated with tau pathology in several tauopathies. J Neuropathol Exp Neurol 70:578–587. 10.1097/NEN.0b013e3182204414 DOI: 10.1097/NEN.0b013e3182204414
Nagy Z, Esiri MM, Cato AM, Smith AD (1997) Cell cycle markers in the hippocampus in Alzheimer’s disease. Acta Neuropathol (Berl) 94:6–15
Nagy Z, Esiri MM (1998) Neuronal cyclin expression in the hippocampus in temporal lobe epilepsy. Exp Neurol 150:240–247. 10.1006/exnr.1997.6753 DOI: 10.1006/exnr.1997.6753
Fiala M, Avagyan H, Merino JJ et al (2013) Chemotactic and mitogenic stimuli of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy. Pathophysiology 20:59–69. 10.1016/j.pathophys.2012.02.003 DOI: 10.1016/j.pathophys.2012.02.003
Husseman JW, Nochlin D, Vincent I (2000) Mitotic activation: a convergent mechanism for a cohort of neurodegenerative diseases. Neurobiol Aging 21:815–828. 10.1016/S0197-4580(00)00221-9 DOI: 10.1016/S0197-4580(00)00221-9
Fielder E, von Zglinicki T, Jurk D (2017) The DNA damage response in neurons: die by apoptosis or survive in a senescence-like state? J Alzheimers Dis JAD 60:S107–S131. 10.3233/JAD-161221 DOI: 10.3233/JAD-161221
