揭示驱动蛋白-1、tau 和微管在阿尔茨海默病相关神经变性中的相互作用

IF 4.2 3区 医学 Q2 NEUROSCIENCES
Frontiers in Cellular Neuroscience Pub Date : 2024-10-23 eCollection Date: 2024-01-01 DOI:10.3389/fncel.2024.1432002
Siva Sundara Kumar Durairajan, Karthikeyan Selvarasu, Abhay Kumar Singh, Supriti Patnaik, Ashok Iyaswamy, Yogini Jaiswal, Leonard L Williams, Jian-Dong Huang
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引用次数: 0

摘要

阿尔茨海默病(AD)的特征是中枢神经系统的神经细胞随着年龄的增长而逐渐退化。在受阿尔茨海默病影响的大脑中观察到的组织病理学特征是细胞外和细胞内淀粉样蛋白-β的异常堆积,以及由过度磷酸化的tau蛋白组成的神经纤维缠结的形成。轴突运输是货物沿轴突移动的基本过程,依赖于驱动蛋白和动力蛋白等分子马达。驱动蛋白负责在神经元内运输重要的货物,因此它的功能障碍与在 AD 中观察到的轴突运输受损有关。轴突运输受损、分子马达蛋白功能障碍以及信号通路失调是导致突触受损和认知能力下降的重要原因。微管相关蛋白 tau 的失调是一个核心因素,它破坏了微管的稳定性并干扰了驱动蛋白-1 的运输。驱动蛋白-1 超家族成员,包括驱动蛋白家族成员 5A、5B 和 5C,以及驱动蛋白轻链,与 AD 病理学有着错综复杂的联系。然而,驱动蛋白家族成员在 AD 患者中的含量并不一致,因此有必要进一步探讨这些运动蛋白对神经退行性病变和轴突运输障碍的机理影响。这篇综述强调了驱动蛋白-1 在 AD 中逆行运输的重要性。它强调了研究运动蛋白对各种神经系统疾病影响的潜在机制的必要性。尽管目前的科学文献还存在局限性,但我们的研究主张以驱动蛋白和自噬功能障碍为靶点,将其作为对 AD 进行新型治疗干预和诊断的可行途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unraveling the interplay of kinesin-1, tau, and microtubules in neurodegeneration associated with Alzheimer's disease.

Alzheimer's disease (AD) is marked by the gradual and age-related deterioration of nerve cells in the central nervous system. The histopathological features observed in the brain affected by AD are the aberrant buildup of extracellular and intracellular amyloid-β and the formation of neurofibrillary tangles consisting of hyperphosphorylated tau protein. Axonal transport is a fundamental process for cargo movement along axons and relies on molecular motors like kinesins and dyneins. Kinesin's responsibility for transporting crucial cargo within neurons implicates its dysfunction in the impaired axonal transport observed in AD. Impaired axonal transport and dysfunction of molecular motor proteins, along with dysregulated signaling pathways, contribute significantly to synaptic impairment and cognitive decline in AD. Dysregulation in tau, a microtubule-associated protein, emerges as a central player, destabilizing microtubules and disrupting the transport of kinesin-1. Kinesin-1 superfamily members, including kinesin family members 5A, 5B, and 5C, and the kinesin light chain, are intricately linked to AD pathology. However, inconsistencies in the abundance of kinesin family members in AD patients underline the necessity for further exploration into the mechanistic impact of these motor proteins on neurodegeneration and axonal transport disruptions across a spectrum of neurological conditions. This review underscores the significance of kinesin-1's anterograde transport in AD. It emphasizes the need for investigations into the underlying mechanisms of the impact of motor protein across various neurological conditions. Despite current limitations in scientific literature, our study advocates for targeting kinesin and autophagy dysfunctions as promising avenues for novel therapeutic interventions and diagnostics in AD.

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来源期刊
CiteScore
7.90
自引率
3.80%
发文量
627
审稿时长
6-12 weeks
期刊介绍: Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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