Research ArticleNeurodegeneration

Manganese promotes the aggregation and prion-like cell-to-cell exosomal transmission of α-synuclein

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Science Signaling  12 Mar 2019:
Vol. 12, Issue 572, eaau4543
DOI: 10.1126/scisignal.aau4543

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Manganese in Parkinson’s disease

Manganese is an essential mineral, but chronic exposure to high amounts of it, such as is experienced by welders, is associated with symptoms of Parkinson’s disease. A hallmark of the disease is aggregation of the protein α-synuclein (αSyn), which is toxic to neurons. Harischandra et al. found that extracellular vesicles called exosomes isolated from serum collected from welders contained misfolded αSyn. In cell culture and mouse models, exposure to manganese or to isolated, manganese-induced exosomes promoted the transfer of αSyn between neurons and microglia, which induced inflammation and neuronal cell death. These findings further explain the role of manganese in neurodegenerative disease.