通过消融模型探索α-Syn的功能:生理和病理意义。

IF 3.6 4区 医学 Q3 CELL BIOLOGY
Anjali Praveen, Godfried Dougnon, Hideaki Matsui
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引用次数: 0

摘要

α-突触核蛋白(α-Syn/SNCA)在帕金森病(PD)的病理生理中起着重要作用,这是神经退行性研究的一个重大进展。几十年后,人们仍在广泛探索这种蛋白质对各种脑部疾病的重大影响。在疾病状态下,α-Syn错误折叠并形成异常聚集体积聚在神经元中,从而引发各种细胞器功能障碍,最终导致神经变性。这些错误折叠的形式是高度异质性的,并且在不同的突触核蛋白病(如PD、多系统萎缩或路易体痴呆)中差异很大。虽然最初认为α-Syn只局限于大脑,但大量证据表明α-Syn的功能超越了中枢神经系统,在外周功能中发挥作用,如免疫反应的调节、造血和胃肠调节。在这里,我们的目标是提供细胞功能和病理表型在体外和体内α-Syn功能衰减时改变的详细编译,并通过细胞和动物模型探索SNCA基因沉默在健康和疾病状态下的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exploring α-Syn's Functions Through Ablation Models: Physiological and Pathological Implications.

A significant advancement in neurodegenerative research was the discovery that α-synuclein (α-Syn/SNCA) plays a part in the pathophysiology of Parkinson's disease (PD). Decades later, the protein's significant impacts on various brain disorders are still being extensively explored. In disease conditions, α-Syn misfolds and forms abnormal aggregates that accumulate in neurons, thus triggering various organellar dysfunctions and ultimately neurodegeneration. These misfolded forms are highly heterogeneous and vary significantly among different synucleinopathies, such as PD, Multiple System Atrophy, or Dementia with Lewy bodies. Though initially believed to be exclusively localized in the brain, numerous pieces of evidence suggest that α-Syn functions transcend the central nervous system, with roles in peripheral functions, such as modulation of immune responses, hematopoiesis, and gastrointestinal regulation. Here, we aim to provide a detailed compilation of cellular functions and pathological phenotypes that are altered upon attenuation of α-Syn function in vitro and in vivo and explore the effects of SNCA gene silencing in healthy and disease states using cellular and animal models.

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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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