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细胞骨架传奇:正常生理中的调控与神经退行性疾病中的调节。

Cytoskeleton saga: Its regulation in normal physiology and modulation in neurodegenerative disorders.

机构信息

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India.

出版信息

Eur J Pharmacol. 2022 Jun 15;925:175001. doi: 10.1016/j.ejphar.2022.175001. Epub 2022 May 4.

Abstract

Cells are fundamental units of life. To ensure the maintenance of homeostasis, integrity of structural and functional counterparts is needed to be essentially balanced. The cytoskeleton plays a vital role in regulating the cellular morphology, signalling and other factors involved in pathological conditions. Microtubules, actin (microfilaments), intermediate filaments (IF) and their interactions are required for these activities. Various proteins associated with these components are primary requirements for directing their functions. Disruption of this organization due to faulty genetics, oxidative stress or impaired transport mechanisms are the major causes of dysregulated signalling cascades leading to various pathological conditions like Alzheimer's (AD), Parkinson's (PD), Huntington's disease (HD) or amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP) or any traumatic injury like spinal cord injury (SCI). Novel or conventional therapeutic approaches may be specific or non-specific, targeting either three basic components of the cytoskeleton or various cascades that serve as a cue to numerous pathways like ROCK signalling or the GSK-3β pathway. An enormous number of drugs have been redirected for modulating the cytoskeletal dynamics and thereby may pave the way for inhibiting the progression of these diseases and their complications.

摘要

细胞是生命的基本单位。为了确保维持内稳态,需要在本质上平衡结构和功能对应的完整性。细胞骨架在调节细胞形态、信号转导和其他与病理条件相关的因素方面起着至关重要的作用。微管、肌动蛋白(微丝)、中间丝(IF)及其相互作用是这些活动所必需的。与这些成分相关的各种蛋白质是指导其功能的主要要求。由于遗传缺陷、氧化应激或运输机制受损而导致的这种组织的破坏,是导致各种病理状况(如阿尔茨海默病(AD)、帕金森病(PD)、亨廷顿病(HD)或肌萎缩侧索硬化症(ALS)、遗传性痉挛性截瘫(HSP)或任何创伤性损伤,如脊髓损伤(SCI))的失调信号级联的主要原因。新型或传统的治疗方法可能是特异性或非特异性的,针对细胞骨架的三个基本成分或作为许多途径的线索的各种级联,如 ROCK 信号或 GSK-3β 途径。已经有大量的药物被重新定向用于调节细胞骨架动力学,从而为抑制这些疾病及其并发症的进展铺平了道路。

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