Clearance and deposition of extracellular alpha-synuclein aggregates in microglia.
Abnormal deposition of alpha-synuclein in neurons and glia is implicated in many neurological diseases, such as Parkinson's disease and Dementia with Lewy bodies. Recently, evidence has emerged that this protein and its aggregates are secreted from neuronal cells, and this extracellular protein may contribute to the pathogenic process. Here, we show that all the major brain cell types (neurons, astrocytes, and microglia) are capable of clearing the extracellular alpha-synuclein aggregates by internalization and degradation. Among these cell types, microglia showed the highest rate of degradation. Upon activation by lipopolysaccharide, the degradation of the internalized alpha-synuclein aggregates was slowed, causing protein accumulation in the microglial cytoplasm. These results suggest that microglia may be the major scavenger cells for extracellular alpha-synuclein aggregates in brain parenchyma, and that clearance may be regulated by the activation state of these cells.
Lee
He-Jin
HJ
Department of Biomedical Science and Technology, RCTC, IBST, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
Suk
Ji-Eun
JE
Bae
Eun-Jin
EJ
Lee
Seung-Jae
SJ
D045744:Cell Line, Tumor; D006801:Humans; D017628:Microglia / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
D051844:alpha-Synuclein