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Cdk5 as a Drug Target for Alzheimer’s Disease

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Cyclin Dependent Kinase 5 (Cdk5)

Abstract

Neurofibrillary tangles (NFTs) are a pathological hallmark in the Alzheimer’s disease (AD) brain and are well correlated with progression of the disease. Since NFTs consist mainly of hyperphosphorylated tau, tau kinases have been suggested as drug targets to slow the progression of AD. This notion has further been supported by recent studies showing the importance of tau and its phosphorylation in neurodegeneration and cognitive deficits in animal models. Among the different putative tau kinases, cyclin-dependent kinase 5 (Cdk5) remains an appealing drug target for AD. Activation of Cdk5 in animal models recapitulates many AD features including tau hyperphosphorylation, NFTs, neurodegeneration, cognitive impairments, and increase in Aβ levels. In addition, inhibition of Cdk5 activities is neuroprotective and appears to enhance long-term potentiation and improve learning and memory—all are potential beneficial features for the treatment of AD.

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  1. Neurodegeneration Research, GlaxoSmithKline R&D China, No. 3 Building, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, China

    Lit-Fui Lau

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  1. Lit-Fui Lau
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  2. Carol D. Hicks
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Correspondence to Lit-Fui Lau .

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  1. Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China

    Nancy Y. Ip

  2. Department of Brain and Cognitive Science, Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, MA, USA

    Li-Huei Tsai

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Lau, LF., Hicks, C.D. (2008). Cdk5 as a Drug Target for Alzheimer’s Disease. In: Ip, N.Y., Tsai, LH. (eds) Cyclin Dependent Kinase 5 (Cdk5). Springer, Boston, MA. https://doi.org/10.1007/978-0-387-78887-6_18

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