Pathogenic roles of alpha-synuclein in Parkinson’s disease and multiple system atrophy

Abstract

Alpha-synucleinopathies (α-synucleinopathies) are a diverse group of neurodegenerative diseases comprising Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Although in all these diseases there exist abnormal accumulation of alpha-synuclein (α-syn) aggregates in nerve tissues, the pathological lesions formed by α-syn aggregates and their cellular locations are quite different. In PD and DLB, the hallmark pathological lesions are Lewy bodies (LBs) and Lewy neurites (LNs), which are localized in the neuronal somata and processes. In MSA, the characteristic pathologic structures are glial cytoplasmic inclusions, which are deposited in the cytoplasm of oligodendrocytes. The fact that PD and MSA have distinct pathological α-syn lesions suggest that different mechanisms play a role in the pathogenesis of the two diseases. In this review article, we compare the clinical manifestations and pathological features of PD and MSA, the two common synucleinopathies, and discuss the potential mechanisms for the formation of α-syn aggregates and their pathologic roles in PD and MSA.

Keywords

alpha-synucleinopathy (α-synucleinopathies) / alpha-synuclein (α-syn) / Parkinson’s disease (PD) / multiple system atrophy (MSA)