Kim Tieu, Ph.D.
Florida International University
NIEHS grantees found that microglia, the main resident immune cells in the brain, are involved in cell-to-cell transmission of the protein alpha-synuclein through the release of exosomes, which are small membrane-bound structures secreted by cells. Accumulation of alpha-synuclein in the brain is a prominent feature in Parkinson’s disease, a disorder of the central nervous system.
Neurons are fundamental cells of the brain and nervous system. When researchers treated neurons with alpha-synuclein, they observed that the protein was packaged into exosomes and released by microglia, triggering protein aggregation. When exosomes were combined with microglial proinflammatory cytokines, which are small proteins secreted by immune cells, these exosomes further increased alpha-synuclein aggregation in neurons.
Next, the researchers found that in mice, a single injection of synthetic alpha-synuclein was followed by cell-to-cell transmission of alpha-synuclein and abnormal aggregation in the mouse brain. By depleting microglia in the mice, the team was able to drastically suppress alpha-synuclein transmission. The researchers also purified microglia-derived exosomes from Parkinson’s disease patients and confirmed that they contained alpha-synuclein. In the lab, the patients’ microglial exosomes were capable of inducing alpha-synuclein aggregation in human neurons.
According to the authors, the study supports the view that microglial exosomes contribute to the progression of alpha-synuclein accumulation and therefore, they may serve as a promising therapeutic target for Parkinson’s disease.
Citation: Guo M, Wang J, Zhao Y, Feng Y, Han S, Dong Q, Cui M, Tieu K. 2020. Microglial exosomes facilitate alpha-synuclein transmission in Parkinson’s disease. Brain 143(5):1476–1497.