Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein
| Autor: | Mi-Young Song, Seokjoong Kim, Seung-Jae Lee, Eliezer Masliah, Byung Chul Jung, Jun Sung Lee, Na Young Yang, He Jin Lee, Sergio Pablo Sardi, Eun Jin Bae, Cheol Soon Lee |
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| Rok vydání: | 2014 |
| Předmět: |
Synucleinopathies
Alpha-synuclein Cell signaling Multidisciplinary animal diseases Cell General Physics and Astronomy Endogeny General Chemistry Biology General Biochemistry Genetics and Molecular Biology Exocytosis nervous system diseases Cell biology chemistry.chemical_compound medicine.anatomical_structure nervous system chemistry Biochemistry Cell culture mental disorders medicine Glucocerebrosidase |
| Zdroj: | NATURE COMMUNICATIONS(5) |
| ISSN: | 2041-1723 |
| Popis: | Deposition of alpha-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 alpha-synuclein aggregates is associated with the progression of PD, the mechanism by which alpha-synuclein aggregates spread remains undefined. Here, we show that alpha-synuclein aggregates are transmitted from cell to cell through a cycle involving uptake of external aggregates, co-aggregation with endogenous alpha-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 alpha-synuclein aggregates. These studies define how alpha-synuclein aggregates spread among neuronal cells and may provide an explanation for how glucocerebrosidase mutations increase the risk of developing PD and other synucleinopathies. |
| Databáze: | OpenAIRE |
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