Neuropathology of Multiple System Atrophy, a Glioneuronal Degenerative Disease
Neuropathology of Multiple System Atrophy, a Glioneuronal Degenerative Disease
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DOI：
10.1007/s12311-022-01407-2
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发表时间：
2022-04-26
期刊：
影响因子：
3.5
通讯作者：
Mori，Fumiaki
中科院分区：
文献类型：
--
作者：
Wakabayashi，Koichi;Miki，Yasuo;Mori，Fumiaki
多系统萎缩（MSA）是一种致死性疾病，其病理特征是被称为胶质细胞质内含物（GCIs）的少突胶质细胞中广泛存在聚集的α-突触核蛋白。α-突触核蛋白聚集体也存在于少突胶质细胞核、神经元细胞质和细胞核中。目前尚不清楚gci中α-突触核蛋白的主要来源是神经元还是少突胶质细胞。越来越多的证据表明，这种疾病有两种退行性过程。一种可能性是，许多gci与寡髓鞘-轴突-神经元复合物的损伤有关，另一种可能性是，神经元包涵病理也是早期的主要事件。少突胶质细胞和神经元可能主要在MSA中受到影响，一种细胞的损伤会导致另一种细胞的退化。囊泡介导的转运在α-突触核蛋白的核转运以及胶质和神经元α-突触核蛋白包涵体的形成中起着关键作用。最近的研究表明，自噬损伤可伴随α-突触核蛋白在MSA和路易体病脑内的积累而发生或作为α-突触核蛋白积累的结果。活化的自噬可能与α-突触核蛋白病的治疗方法有关。
Multiple system atrophy (MSA) is a fatal disease characterized pathologically by the widespread occurrence of aggregated α-synuclein in the oligodendrocytes referred to as glial cytoplasmic inclusions (GCIs). α-Synuclein aggregates are also found in the oligodendroglial nuclei and neuronal cytoplasm and nuclei. It is uncertain whether the primary source of α-synuclein in GCIs is originated from neurons or oligodendrocytes. Accumulating evidence suggests that there are two degenerative processes in this disease. One possibility is that numerous GCIs are associated with the impairment of oligo-myelin-axon-neuron complex, and the other is that neuronal inclusion pathology is also a primary event from the early stage. Both oligodendrocytes and neurons may be primarily affected in MSA, and the damage of one cell type contributes to the degeneration of the other. Vesicle-mediated transport plays a key role in the nuclear translocation of α-synuclein as well as in the formation of glial and neuronal α-synuclein inclusions. Recent studies have shown that impairment of autophagy can occur along with or as a result of α-synuclein accumulation in the brain of MSA and Lewy body disease. Activated autophagy may be implicated in the therapeutic approach for α-synucleinopathies.