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

Research output: Contribution to journalArticle

72 Citations (Scopus)

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.

Original languageEnglish
Article number4755
JournalNature Communications
Volume5
DOIs
StatePublished - 26 Aug 2014

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Synucleins
Glucosylceramidase
depletion
Parkinson disease
Parkinson Disease
cells
peripheral nervous system
Exocytosis
Peripheral Nervous System
central nervous system
impairment
Neurology
mutations
progressions
Central Nervous System
Agglomeration
Mutation

Cite this

Bae, Eun Jin ; Yang, Na Young ; Song, Miyoung ; Lee, Cheol Soon ; Lee, Jun Sung ; Jung, Byung Chul ; Lee, He Jin ; Kim, Seokjoong ; Masliah, Eliezer ; Sardi, Sergio Pablo ; Lee, Seung-Jae. / Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein. In: Nature Communications. 2014 ; Vol. 5.
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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.",
author = "Bae, {Eun Jin} and Yang, {Na Young} and Miyoung Song and Lee, {Cheol Soon} and Lee, {Jun Sung} and Jung, {Byung Chul} and Lee, {He Jin} and Seokjoong Kim and Eliezer Masliah and Sardi, {Sergio Pablo} and Seung-Jae Lee",
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Bae, EJ, Yang, NY, Song, M, Lee, CS, Lee, JS, Jung, BC, Lee, HJ, Kim, S, Masliah, E, Sardi, SP & Lee, S-J 2014, 'Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein', Nature Communications, vol. 5, 4755. https://doi.org/10.1038/ncomms5755

Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein. / Bae, Eun Jin; Yang, Na Young; Song, Miyoung; Lee, Cheol Soon; Lee, Jun Sung; Jung, Byung Chul; Lee, He Jin; Kim, Seokjoong; Masliah, Eliezer; Sardi, Sergio Pablo; Lee, Seung-Jae.

In: Nature Communications, Vol. 5, 4755, 26.08.2014.

Research output: Contribution to journalArticle

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AU - Bae, Eun Jin

AU - Yang, Na Young

AU - Song, Miyoung

AU - Lee, Cheol Soon

AU - Lee, Jun Sung

AU - Jung, Byung Chul

AU - Lee, He Jin

AU - Kim, Seokjoong

AU - Masliah, Eliezer

AU - Sardi, Sergio Pablo

AU - Lee, Seung-Jae

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