title: The Role of Cdk5 in Alzheimer's Disease.
abstract: Alzheimer's disease (AD) is known as the most fatal chronic neurodegenerative disease in adults along with progressive loss of memory and other cognitive function disorders. Cyclin-dependent kinase 5 (Cdk5), a unique member of the cyclin-dependent kinases (Cdks), is reported to intimately associate with the process of the pathogenesis of AD. Cdk5 is of vital importance in the development of CNS and neuron movements such as neuronal migration and differentiation, synaptic functions, and memory consolidation. However, when neurons suffer from pathological stimuli, Cdk5 activity becomes hyperactive and causes aberrant hyperphosphorylation of various substrates of Cdk5 like amyloid precursor protein (APP), tau and neurofilament, resulting in neurodegenerative diseases like AD. Deregulation of Cdk5 contributes to an array of pathological events in AD, ranging from formation of senile plaques and neurofibrillary tangles, synaptic damage, mitochondrial dysfunction to cell cycle reactivation as well as neuronal cell apoptosis. More importantly, an inhibition of Cdk5 activity with inhibitors such as RNA inference (RNAi) could protect from memory decline and neuronal cell loss through suppressing β-amyloid (Aβ)-induced neurotoxicity and tauopathies. This review will briefly describe the above-mentioned possible roles of Cdk5 in the physiological and pathological mechanisms of AD, further discussing recent advances and challenges in Cdk5 as a therapeutic target.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Shu-Lei
authors.initials: SL
authors.lastname: Liu
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology, Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China. dr.tanlan@163.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Geriatrics, The Affiliated Hospital of Qingdao University, Qingdao, China. xingang2005@sina.com.
authors.forename: Ang
authors.initials: A
authors.lastname: Xing
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China. yu-jintai@163.com.|Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA. yu-jintai@163.com.
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D000818:Animals; D017209:Apoptosis; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009473:Neuronal Plasticity
chemical_list: D051360:Cyclin-Dependent Kinase 5
keywords: Alzheimer’s disease; Aβ; Cdk5; Pathogenesis; Tau; Therapy