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The Role of Cdk5 in Alzheimer’s Disease

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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.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81471309, 81371406, 81171209), the Shandong Provincial Outstanding Medical Academic Professional Program, Qingdao Key Health Discipline Development Fund, Qingdao Outstanding Health Professional Development Fund, and Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders.

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The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China

    Shu-Lei Liu, Chong Wang, Lan Tan & Jin-Tai Yu

  2. Department of Neurology, Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China

    Teng Jiang

  3. Department of Geriatrics, The Affiliated Hospital of Qingdao University, Qingdao, China

    Ang Xing

  4. Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA

    Jin-Tai Yu

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  1. Shu-Lei Liu
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  2. Chong Wang
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  3. Teng Jiang
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  4. Lan Tan
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  5. Ang Xing
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  6. Jin-Tai Yu
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Corresponding authors

Correspondence to Lan Tan, Ang Xing or Jin-Tai Yu.

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Liu, SL., Wang, C., Jiang, T. et al. The Role of Cdk5 in Alzheimer’s Disease. Mol Neurobiol 53, 4328–4342 (2016). https://doi.org/10.1007/s12035-015-9369-x

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  • DOI: https://doi.org/10.1007/s12035-015-9369-x

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