Abstract：
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.
摘要：
阿尔茨海默病(Alzheimer\'sdisease,AD)仍然是世界范围内最具挑战性和最普遍的神经退行性疾病之一。尽管进行了广泛的研究，缺乏有效的AD治疗方法，强调需要更深入地了解其潜在的分子机制。细胞周期蛋白依赖性激酶5（CDK5），丝氨酸/苏氨酸激酶主要与细胞周期调节和神经元发育有关，已成为AD病理学的关键角色。本文就CDK5在AD发病机制中的多方面作用进行综述。我们首先阐明CDK5在正常大脑发育和神经元维持中的生理功能，强调它参与突触可塑性，神经递质释放，和细胞骨架动力学。随后，我们深入研究了在AD中观察到的CDK5活性失调，包括异常的过度激活，和失调的蛋白质相互作用。此外，我们讨论了CDK5和AD相关蛋白之间的复杂相互作用，包括淀粉样β前体蛋白（APP）和tau蛋白，阐明它们对疾病进展的集体影响。最后,我们描述了可用于抑制CDK-5的各种方法,这些方法可作为AD的未来治疗干预进行探索.通过综合体外研究的证据，动物模型,和临床调查，本文综述了CDK5失调与AD发病机制之间错综复杂的关系,提供可能为未来治疗干预策略提供信息的见解。
