455
Views
18
CrossRef citations to date
0
Altmetric
Original Articles

Cdk5: A main culprit in neurodegeneration

&
Pages 1192-1197 | Received 04 Mar 2019, Accepted 11 Jul 2019, Published online: 13 Sep 2019

References

  • Malumbres M, Harlow E, Hunt T, et al. Cyclin-dependent kinases: a family portrait. Nat Cell Biol. 2009;11:1275–1276.
  • Chang KH, Vincent F, Shah K. Deregulated Cdk5 triggers aberrant activation of cell cycle kinases and phosphatases inducing neuronal death. J Cell Sci. 2012;125:5124–5137.
  • Shukla AK, Spurrier J, Kuzina I, et al. Hyperactive innate immunity causes degeneration of dopamine neurons upon altering activity of Cdk5. Cell Rep. 2019;26:131–144.e4.
  • Tsai LH, Delalle I, Caviness VS Jr, et al. p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. Nature. 1994;371:419–423.
  • Pérez-Morales J, Mejías-Morales D, Rivera-Rivera S, et al. Hyper-phosphorylation of Rb S249 together with CDK5R2/p39 overexpression areassociated with impaired cell adhesion and epithelial-to-mesenchymal transition: implications as a potential lungcancer grading and staging biomarker. PLoS One. 2018;13(11):e0207483.
  • Tang D, Yeung J, Lee KY, et al. An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) activator. J Biol Chem. 1995;270:26897–26903.
  • Ohshima T, Ward JM, Huh CG, et al. Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Proc Natl Acad Sci U S A. 1996;93:11173–11178.
  • Bibb JA, Chen J, Taylor JR, et al. Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5. Nature. 2001;410:376–380.
  • Fischer A, Sananbenesi F, Schrick C, et al. Cyclin-dependent kinase 5 is required for associative learning. J Neurosci. 2002;22:3700–3707.
  • Cruz JC, Tseng HC, Goldman JA, et al. Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles. Neuron. 2003;40:471–483.
  • Qu D, Rashidian J, Mount MP, et al. Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson's disease. Neuron. 2007;55:37–52.
  • Patrick GN, Zukerberg L, Nikolic M, et al. Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature. 1999;402:615–622.
  • Takahashi S, Ohshima T, Hirasawa M, et al. Conditional deletion of neuronal cyclin-dependent kinase 5 in developing forebrain results in microglial activation and neurodegeneration. Am J Pathol. 2010;176:320–329.
  • Cheung ZH, Ip NY. Cdk5: a multifaceted kinase in neurodegenerative diseases. Trends Cell Biol. 2012;22:169–175.
  • Tarricone C, Dhavan R, Peng J, et al. Structure and regulation of the CDK5-p25(nck5a) complex. Mol Cell. 2001;8:657–669.
  • Saito K, Elce JS, Hamos JE, et al. Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration. Proc Natl Acad Sci U S A. 1993;90:2628–2632.
  • Nixon RA. The calpains in aging and aging-related diseases. Ageing Res Rev. 2003;2:407–418.
  • Sato K, Minegishi S, Takano J, et al. Calpastatin, an endogenous calpain-inhibitor protein, regulates the cleavage of the Cdk5 activator p35 to p25. J Neurochem. 2011;117:504–515.
  • Kamei H, Saito T, Ozawa M, et al. Suppression of calpain-dependent cleavage of the CDK5 activator p35 to p25 by site-specific phosphorylation. J Biol Chem. 2007;282:1687–1694.
  • He L, Hou Z, Qi RZ. Calmodulin binding and Cdk5 phosphorylation of p35 regulate its effect on microtubules. J Biol Chem. 2008;283:13252–13260.
  • Shah K, Lahiri DK. Cdk5 activity in the brain - multiple paths of regulation. J Cell Sci. 2014;127:2391–2400.
  • Ledee DR, Gao CY, Seth R, et al. A specific interaction between muskelin and the cyclin-dependent kinase 5 activator p39 promotes peripheral localization of muskelin. J Biol Chem. 2005;280:21376–21383.
  • Ko J, Humbert S, Bronson RT, et al. p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment. J Neurosci. 2001;21:6758–6771.
  • Modi PK, Komaravelli N, Singh N, et al. Interplay between MEK-ERK signaling, cyclin D1, and cyclin-dependent kinase 5 regulates cell cycle reentry and apoptosis of neurons. Mol Biol Cell. 2012;23:3722–3730.
  • Odajima J, Wills ZP, Ndassa YM, et al. Cyclin E constrains Cdk5 activity to regulate synaptic plasticity and memory formation. Dev Cell. 2011;21:655–668.
  • Brinkkoetter PT, Olivier P, Wu JS, et al. Cyclin I activates Cdk5 and regulates expression of Bcl-2 and Bcl-XL in postmitotic mouse cells. J Clin Invest. 2009;119:3089–3101.
  • Sun KH, Chang KH, Clawson S, et al. Glutathione-S-transferase P1 is a critical regulator of Cdk5 kinase activity. J Neurochem. 2011;118:902–914.
  • Berhane K, Widersten M, Engström A, et al. Detoxication of base propenals and other alpha, beta-unsaturated aldehyde products of radical reactions and lipid peroxidation by human glutathione transferases. Proc Natl Acad Sci U S A. 1994;91:1480–1484.
  • Lee JH, Kim KT. Induction of cyclin-dependent kinase 5 and its activator p35 through the extracellular-signal-regulated kinase and protein kinase A pathways during retinoic-acid mediated neuronal differentiation in human neuroblastoma SK-N-BE(2)C cells. J Neurochem. 2004;91:634–647.
  • Absalon S, Kochanek DM, Raghavan V, et al. MiR-26b, upregulated in Alzheimer's disease, activates cell cycle entry, tau-phosphorylation, and apoptosis in postmitotic neurons. J Neurosci. 2013;33:14645–14659.
  • Zukerberg LR, Patrick GN, Nikolic M, et al. Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth. Neuron. 2000;26:633–646.
  • Sasaki Y, Cheng C, Uchida Y, et al. Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex. Neuron. 2002;35:907–920.
  • Cheng Q, Sasaki Y, Shoji M, et al. Cdk5/p35 and Rho-kinase mediate ephrin-A5-induced signaling in retinal ganglion cells. Mol Cell Neurosci. 2003;24:632–645.
  • Lin H, Lin TY, Juang JL. Abl deregulates Cdk5 kinase activity and subcellular localization in Drosophila neurodegeneration. Cell Death Differ. 2007;14:607–615.
  • Cancino GI, Perez de Arce K, Castro PU, et al. c-Abl tyrosine kinase modulates tau pathology and Cdk5 phosphorylation in AD transgenic mice. Neurobiol Aging. 2011;32:1249–1261.
  • Qu J, Nakamura T, Cao G, et al. S-Nitrosylation activates Cdk5 and contributes to synaptic spine loss induced by beta-amyloid peptide. Proc Natl Acad Sci USA. 2011;108:14330–14335.
  • Zhang P, Yu PC, Tsang AH, et al. S-nitrosylation of cyclin-dependent kinase 5 (cdk5) regulates its kinase activity and dendrite growth during neuronal development. J Neurosci. 2010;30:14366–14370.
  • Ohshima T, Ogura H, Tomizawa K, et al. Impairment of hippocampal long-term depression and defective spatial learning and memory in p35 mice. J Neurochem. 2005;94:917–925.
  • Guan JS, Su SC, Gao J, et al. Cdk5 is required for memory function and hippocampal plasticity via the cAMP signaling pathway. PLoS One. 2011;6:e25735.
  • Hawasli A, Benavides DR, Nguyen C, et al. Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation. Nat Neurosci. 2007;10:880–886.
  • Pareek TK, Keller J, Kesavapany S, et al. Cyclin-dependent kinase 5 activity regulates pain signaling. Proc Natl Acad Sci U S A. 2006;103:791–796.
  • Pareek TK, Keller J, Kesavapany S, et al. Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1. Proc Natl Acad Sci U S A. 2007;104:660–665.
  • Nagy P, Varga Á, Kovács AL, et al. How and why to study autophagy in Drosophila: it's more than just a garbage chute. Methods. 2015;75:151–161.
  • Mauvezin C, Nagy P, Juhász G, et al. Autophagosome-lysosome fusion is independent of V-ATPase-mediated acidification. Nat Commun. 2015;6:7007.
  • Spurrier J, Shukla AK, McLinden K, et al. Altered expression of the Cdk5 activator-like protein. Cdk5α, causes neurodegeneration, in part by accelerating the rate of aging. Dis Model Mech. 2018;11:dmm031161.
  • Nandi N, Tyra LK, Stenesen D, et al. Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in Drosophila melanogaster by phosphorylating acinus at serine437. Elife. 2017;6:e30760.
  • Lee HK, Lund JM, Ramanathan B, et al. Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science. 2007;315:1398–1401.
  • Anglade P, Vyas S, Javoy-Agid F, et al. Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease. Histol Histopathol. 1997;12:25–31.
  • Narendra DP, Jin SM, Tanaka A, et al. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 2010;8:e1000298.
  • Kannarkat GT, Boss JM, Tansey MG. The role of innate and adaptive immunity in Parkinson's disease. J Parkinsons Dis. 2013;3:493–514.
  • Gjoneska E, Pfenning AR, Mathys H, et al. Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer's disease. Nature. 2015;518:365–369.
  • Wen Y, Yu WH, Maloney B, et al. Transcriptional regulation of beta-secretase by p25/cdk5 leads to enhanced amyloidogenic processing. Neuron. 2008;57:680–690.
  • Glicksman MA1, Cuny GD, Liu M, et al. New approaches to the discovery of cdk5 inhibitors. Curr Alzheimer Res. 2007;4:547–549.
  • Zhu JH, Guo F, Shelburne J, et al. Localization of phosphorylated ERK/MAP kinases to mitochondria and autophagosomes in Lewy body diseases. Brain Pathol. 2003;13:473–481.
  • Menn B, Bach S, Blevins TL, et al. Delayed treatment with systemic (S)-roscovitine provides neuroprotection and inhibits in vivo CDK5 activity increase in animal stroke models. PLoS One. 2010;5:e12117.
  • Mueller BK, Mack H, Teusch N. Rho kinase, a promising drug target for neurological disorders. Nat Rev Drug Discov. 2005;4:387–398.
  • Kaur C, Ling EA. Microglia-a therapeutic target in neurological diseases and disorders. CNS Neurol Disord Drug Targets. 2013;12:719.
  • Kinch MS. An analysis of FDA-approved drugs for neurological disorders. Drug Discov Today. 2015;20:1040–1043.
  • Sharma S, Taliyan R, Sarathlal KC. Epigenetics in neurodegenerative diseases: the role of histone deacetylases. CNS Neurol Disord Drug Targets. 2018;18(1):11–18.
  • van Leyen K. Lipoxygenase: an emerging target for stroke therapy. CNS Neurol Disord Drug Targets. 2013;12:191–199.
  • Vassar R. BACE1: the beta-secretase enzyme in Alzheimer's disease. J Mol Neurosci. 2004;23:105–114.
  • Zhang L, Liu W, Szumlinski KK, et al. p10, the N-terminal domain of p35, protects against CDK5/p25-induced neurotoxicity. Proc Natl Acad Sci USA. 2012;109:20041–20046.
  • Zheng YL, Li BS, Amin ND, et al. A peptide derived from cyclin-dependent kinase activator (p35) specifically inhibits Cdk5 activity and phosphorylation of tau protein in transfected cells. Eur J Biochem. 2002;269:4427–4434.
  • Sundaram JR, Poore CP, Sulaimee NH, et al. Specific inhibition of p25/Cdk5 activity by the Cdk5 inhibitory peptide reduces neurodegeneration in vivo. J Neurosci. 2013;33:334–343.
  • Tripathi SK, Muttineni R, Singh SK. Extra precision docking, free energy calculation and molecular dynamics simulation studies of CDK2 inhibitors. J Theor Biol. 2013;334:87–100.
  • Singh SK, Dessalew N, Bharatam PV. 3D-QSAR CoMFA study on indenopyrazole derivatives as cyclin dependent kinase 4 (CDK4) and cyclin dependent kinase 2 (CDK2) inhibitors. Eur J Med Chem. 2006;41:1310–1319.
  • Tripathi SK, Singh SK. Insights into the structural basis of 3, 5-diaminoindazoles as CDK2 inhibitors: prediction of binding modes and potency by QM–MM interaction, MESP and MD simulation. Mol Biosyst. 2014;10:2189–2201.
  • Tripathi SK, Singh SK, Singh P, et al. Exploring the selectivity of a ligand complex with CDK2/CDK1: a molecular dynamics simulation approach. J Mol Recognit. 2012;25:504–512.
  • Karthiga A, Tripathi SK, Shanmugam R, et al. Targeting the cyclin-binding groove site to inhibit the catalytic activity of CDK2/cyclin A complex using p27(KIP1)-derived peptidomimetic inhibitors. J Chem Biol. 2015;8:11–24.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.