[HTML][HTML] Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein

EJ Bae, NY Yang, M Song, CS Lee, JS Lee… - Nature …, 2014 - nature.com
EJ Bae, NY Yang, M Song, CS Lee, JS Lee, BC Jung, HJ Lee, S Kim, E Masliah, SP Sardi
Nature communications, 2014nature.com
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 …
Abstract
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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