Activated microglia facilitate the transmission of α-synuclein in Parkinson's disease

Abstract

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and abnormal aggregates of α-synuclein protein called Lewy bodies. To date, there is no drug that can definitely slow down or stop the progression of this disease. The discovery of the cell-to-cell transmission of pathologic α-synuclein seeds offers the possibility to explore novel treatment strategies to prevent the spread of α-synuclein, with the purpose of slowing down the progression of PD in its tracks. Although recent studies have made tremendous progress in understanding how α-synuclein spreads throughout the brain, neuroinflammation seems to play a crucial role in the development of α-synuclein pathology in PD. The activation of microglia, one of the hallmarks of the neuroinflammatory process, is suggested to influence the neuron-to-neuron transmission of α-synuclein. This review summarizes how activated microglia facilitate this process, and focuses on the following mechanisms including the activation of microglia in PD, the reduced ability of activated microglia to clear α-synuclein and increased migratory capacity of microglia in PD, as well as the cooperation between microglia and exosomes in mediating α-synuclein release and propagation. In conclusion, this article help collate information on microglia in-relation to PD.

Keywords: Microglia; Neuroinflammation; Parkinson's disease (PD); α-synuclein; α-synuclein propagation.