Erythrocytic α-synuclein contained in microvesicles regulates astrocytic glutamate homeostasis: a new perspective on Parkinson’s disease pathogenesis

Autor: Lifu Sheng, Tessandra Stewart, Dishun Yang, Eric Thorland, David Soltys, Patrick Aro, Tarek Khrisat, Zhiying Xie, Na Li, Zongran Liu, Chen Tian, Matthew Bercow, Junichi Matsumoto, Cyrus P. Zabetian, Elaine Peskind, Joseph F. Quinn, Min Shi, Jing Zhang
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Acta Neuropathologica Communications, Vol 8, Iss 1, Pp 1-22 (2020)
Druh dokumentu: article
ISSN: 2051-5960
DOI: 10.1186/s40478-020-00983-w
Popis: Abstract Parkinson’s disease is a neurodegenerative disorder characterized by the transmission and accumulation of toxic species of α-synuclein (α-syn). Extracellular vesicles (EVs) are believed to play a vital role in the spread of toxic α-syn species. Recently, peripheral α-syn pathology has been investigated, but little attention has been devoted to erythrocytes, which contain abundant α-syn. In this study, we first demonstrated that erythrocyte-derived EVs isolated from Parkinson’s disease patients carried elevated levels of oligomeric α-syn, compared to those from healthy controls. Moreover, human erythrocyte-derived EVs, when injected into peripheral blood in a mouse model of Parkinson’s disease, were found to readily cross the blood-brain barrier (BBB). These EVs accumulated in astrocyte endfeet, a component of the BBB, where they impaired glutamate uptake, likely via interaction between excitatory amino acid transporter 2 (EAAT2) and oligomeric α-syn. These data suggest that erythrocyte-derived EVs and the oligomeric α-syn carried in them may play critical roles in the progression or even initiation of Parkinson’s disease. Additionally, the mechanisms involved are attributable at least in part to dysfunction of astrocytes induced by these EVs. These observations provide new insight into the understanding of the mechanisms involved in Parkinson’s disease.
Databáze: Directory of Open Access Journals
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