The p35/CDK5 active complex plays a fundamental role in brain development and functioning, but its deregulated activity has also been implicated in various neurodegenerative disorders, including Alzheimer's disease (AD).
This review focuses on the implication of Cdk5 in the signaling pathways of both neurodegenerative diseases and drug abuse, and the mechanism of Cdk5 involvement in insulin secretion.
Together with its essential physiological roles, a major discovery was the finding twenty years ago that CDK5 participates in neurodegenerative diseases responsible for tau hyperphosphorylations, and, as a consequence, it becomes a neurotoxic factor.
Unlike Cdk5/p35, which is important for brain development, aberrant activity of Cdk5/p25 plays a pathological role in neurodegenerative diseases, such as Alzheimer's disease, by inducing hyperphosphorylation of downstream substrates related to pathological progression.