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α-突触核蛋白的朊病毒样传播:从帕金森病的体外到体内模型。

The prion-like spreading of α-synuclein: From in vitro to in vivo models of Parkinson's disease.

机构信息

Unité de Traffic Membranaire et Pathogénèse, Institut Pasteur, Paris, France.

Unité de Traffic Membranaire et Pathogénèse, Institut Pasteur, Paris, France.

出版信息

Ageing Res Rev. 2019 Mar;50:89-101. doi: 10.1016/j.arr.2019.01.012. Epub 2019 Jan 25.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. PD is characterized by the loss of dopaminergic neurons, primarily in brain regions that control motor functions, thereby leading to motor impairments in the patients. Pathological aggregated forms of the synaptic protein, α-synuclein (α-syn), are involved in the generation and progression of PD. In PD brains, α-syn accumulates inside neurons and propagates from cell-to-cell in a prion-like manner. In this review, we discuss the in vitro and in vivo models used to study the prion-like properties of α-syn and related findings. In particular, we focus on the different mechanisms of α-syn spreading, which could be relevant for the development of alternative therapeutic approaches for PD treatment.

摘要

帕金森病(PD)是仅次于阿尔茨海默病的第二常见神经退行性疾病。PD 的特征是多巴胺能神经元的丧失,主要发生在控制运动功能的大脑区域,从而导致患者的运动障碍。突触蛋白α-突触核蛋白(α-syn)的病理性聚集形式参与了 PD 的发生和进展。在 PD 大脑中,α-syn 在内神经元中积累,并以类朊病毒样方式在细胞间传播。在这篇综述中,我们讨论了用于研究 α-syn 类朊病毒特性及其相关发现的体外和体内模型。特别是,我们专注于 α-syn 传播的不同机制,这对于开发 PD 治疗的替代治疗方法可能具有重要意义。

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