Cyclin-dependent kinase 5 (CDK5) is a proline-directed serine/threonine kinase belonging
to the family of cyclin-dependent kinases. In addition to maintaining the neuronal architecture,
CDK5 plays an important role in the regulation of synaptic plasticity, neurotransmitter release, neuron migration and neurite outgrowth.
Although various reports have shown links between neurodegeneration and deregulation of cyclin-dependent kinases, the specific
role of CDK5 inhibition in causing neuroprotection in cases of neuronal insult or in neurodegenerative diseases is not wellunderstood.
This article discusses current evidence for the involvement of CDK5 deregulation in neurodegenerative disorders and neurodegeneration
associated with stroke through various mechanisms. These include upregulation of cyclin D1 and overactivation of CDK5
mediated neuronal cell death pathways, aberrant hyperphosphorylation of human tau proteins and/or neurofilament proteins, formation of
neurofibrillary lesions, excitotoxicity, cytoskeletal disruption, motor neuron death (due to abnormally high levels of CDK5/p25) and colchicine-
induced apoptosis in cerebellar granule neurons. A better understanding of the role of CDK5 inhibition in neuroprotective
mechanisms will help scientists and researchers to develop selective, safe and efficacious pharmacological inhibitors of CDK5 for therapeutic
use against human neurodegenerative disorders, such as Alzheimer’s disease, amyotrophic lateral sclerosis and neuronal loss associated
Keywords: CDK5 inhibitors, neuroprotection, neurodegeneration, β-amyloid, Alzheimer’s disease, tau hyperphosphorylation, ischemic
stroke, synaptic, excitotoxicity, amyotrophic lateral sclerosis.
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