CDK5 as a therapeutic tool for the treatment of Alzheimer's disease: A review.

Autor: Garemilla S; Department of Life Sciences, GITAM School of Sciences, GITAM (Deemed to Be) University, Visakhapatnam, India; The George Washington University, Washington, DC, USA., Kumari R; Department of Life Sciences, GITAM School of Sciences, GITAM (Deemed to Be) University, Visakhapatnam, India; Department of Biotechnology, Savitribai Phule Pune University, Pune, Maharashtra, India., Kumar R; Department of Life Sciences, GITAM School of Sciences, GITAM (Deemed to Be) University, Visakhapatnam, India. Electronic address: rkumar2@gitam.edu.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Sep 05; Vol. 978, pp. 176760. Date of Electronic Publication: 2024 Jun 18.
DOI: 10.1016/j.ejphar.2024.176760
Abstrakt: Alzheimer's disease (AD) remains one of the most challenging and prevalent neurodegenerative disorders worldwide. Despite extensive research efforts, effective treatments for AD are lacking, emphasising the need for a deeper understanding of its underlying molecular mechanisms. Cyclin-dependent kinase 5 (CDK5), a serine/threonine kinase primarily associated with cell cycle regulation and neuronal development, has emerged as a key player in AD pathology. This review article comprehensively explores the multifaceted roles of CDK5 in the pathogenesis of AD. We begin by elucidating the physiological functions of CDK5 in normal brain development and neuronal maintenance, highlighting its involvement in synaptic plasticity, neurotransmitter release, and cytoskeletal dynamics. Subsequently, we delve into the dysregulation of CDK5 activity observed in AD, encompassing aberrant hyperactivation, and dysregulated protein interactions. Moreover, we discuss the intricate interplay between CDK5 and AD-related proteins, including amyloid-beta precursor protein (APP) and tau protein, elucidating their collective impact on disease progression. Finally, we described various approaches available for the inhibition of CDK-5, which can be explored as future therapeutic intervention for AD. Through synthesizing evidence from in vitro studies, animal models, and clinical investigations, this review provides a comprehensive overview of the intricate relationship between CDK5 dysregulation and AD pathogenesis, offering insights that may inform future therapeutic interventions strategies.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: