Erythrocytic α-synuclein contained in microvesicles regulates astrocytic glutamate homeostasis: a new perspective on Parkinson's disease pathogenesis
Autor: | Junichi Matsumoto, Patrick Aro, Min Shi, Eric Thorland, Tessandra Stewart, Tarek Khrisat, Na Li, Zongran Liu, Matthew Bercow, Lifu Sheng, Elaine R. Peskind, Dishun Yang, David Soltys, Chen Tian, Joseph F. Quinn, Jing Zhang, Zhiying Xie, Cyrus P. Zabetian |
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Rok vydání: | 2020 |
Předmět: |
Parkinson's disease
Erythrocytes Glutamic Acid Biology Blood–brain barrier lcsh:RC346-429 Pathology and Forensic Medicine Pathogenesis Alpha-synuclein Cellular and Molecular Neuroscience chemistry.chemical_compound Mice Glutamate homeostasis Cell-Derived Microparticles medicine Animals Homeostasis Humans lcsh:Neurology. Diseases of the nervous system Blood-brain barrier Research Glutamate receptor Parkinson Disease Extracellular vesicles medicine.disease Microvesicles Cell biology nervous system diseases medicine.anatomical_structure chemistry nervous system Astrocytes Disease Progression Parkinson’s disease Neurology (clinical) Glutamate Astrocyte |
Zdroj: | Acta Neuropathologica Communications Acta Neuropathologica Communications, Vol 8, Iss 1, Pp 1-22 (2020) |
ISSN: | 2051-5960 |
Popis: | 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: | OpenAIRE |
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