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各种帕金森病相似形式的神经退行性变机制。

Mechanisms of Neurodegeneration in Various Forms of Parkinsonism-Similarities and Differences.

机构信息

Department of Neurology, Faculty of Heath Science, Medical University of Warsaw, 03-285 Warsaw, Poland.

Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA.

出版信息

Cells. 2021 Mar 16;10(3):656. doi: 10.3390/cells10030656.

Abstract

Parkinson's disease (PD), dementia with Lewy body (DLB), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA) belong to a group of neurodegenerative diseases called parkinsonian syndromes. They share several clinical, neuropathological and genetic features. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Neuronal loss is associated with extra- and intracellular accumulation of misfolded proteins. The parkinsonian diseases affect distinct areas of the brain. PD and MSA belong to a group of synucleinopathies that are characterized by the presence of fibrillary aggregates of α-synuclein protein in the cytoplasm of selected populations of neurons and glial cells. PSP is a tauopathy associated with the pathological aggregation of the microtubule associated tau protein. Although PD is common in the world's aging population and has been extensively studied, the exact mechanisms of the neurodegeneration are still not fully understood. Growing evidence indicates that parkinsonian disorders to some extent share a genetic background, with two key components identified so far: the microtubule associated tau protein gene () and the α-synuclein gene (). The main pathways of parkinsonian neurodegeneration described in the literature are the protein and mitochondrial pathways. The factors that lead to neurodegeneration are primarily environmental toxins, inflammatory factors, oxidative stress and traumatic brain injury.

摘要

帕金森病 (PD)、路易体痴呆 (DLB)、进行性核上性麻痹 (PSP)、皮质基底节变性 (CBD) 和多系统萎缩 (MSA) 属于一组称为帕金森综合征的神经退行性疾病。它们具有一些共同的临床、神经病理学和遗传特征。神经退行性疾病的特征是特定神经元群体的进行性功能障碍,决定了临床表现。神经元丧失与错误折叠蛋白质的细胞内外积累有关。帕金森病影响大脑的不同区域。PD 和 MSA 属于一类突触核蛋白病,其特征是在选定的神经元和神经胶质细胞群体的细胞质中存在 α-突触核蛋白纤维状聚集物。PSP 是一种与微管相关的 tau 蛋白病理性聚集相关的 tau 病。尽管 PD 在世界人口老龄化中很常见且已被广泛研究,但神经退行性变的确切机制仍不完全清楚。越来越多的证据表明,帕金森病在某种程度上具有遗传背景,迄今为止已确定了两个关键成分:微管相关的 tau 蛋白基因 () 和 α-突触核蛋白基因 ()。文献中描述的帕金森神经退行性变的主要途径是蛋白和线粒体途径。导致神经退行性变的因素主要是环境毒素、炎症因子、氧化应激和创伤性脑损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bec8/7999195/3b762e5ff30c/cells-10-00656-g001.jpg

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