Welcome to the blog for the PREDICT-PD project. We are working to understand the risk factors for Parkinson's Disease and blogging about advances made in prediction and early detection of the disease.
Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein
Eun-Jin Bae,
Na-Young Yang,
Miyoung Song,
Cheol Soon Lee,
Jun Sung Lee,
Byung Chul Jung,
He-Jin Lee,
Seokjoong Kim,
Eliezer Masliah,
Sergio Pablo Sardi
& Seung-Jae Lee
Nature Communications
5,
Article number:
4755
doi:10.1038/ncomms5755
Received
Accepted
Published
Deposition of α-synuclein aggregates occurs widely in the central and peripheral nervous systems in Parkinson’s disease (PD). Although recent evidence has suggested that cell-to-cell transmission of α-synuclein aggregates is associated with the progression of PD, the mechanism by which α-synuclein aggregates spread remains undefined. Here, we show that α-synuclein aggregates are transmitted from cell to cell through a cycle involving uptake of external aggregates, co-aggregation with endogenous α-synuclein and exocytosis of the co-aggregates. Moreover, we find that glucocerebrosidase depletion, which has previously been strongly associated with PD and increased cognitive impairment, promotes propagation of α-synuclein aggregates. These studies define how α-synuclein aggregates spread among neuronal cells and may provide an explanation for how glucocerebrosidase mutations increase the risk of developing PD and other synucleinopathies.
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