| Autor: |
Sophia D. Staerz, Charles Anamoah, Jetze J. Tepe |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 27, Iss 7, Pp 110166- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2024.110166 |
| Popis: |
Summary: Synucleinopathies are a class of neurodegenerative diseases defined by the presence of α-synuclein inclusions. The location and composition of these α-synuclein inclusions directly correlate to the disease pattern. The inclusions in Multiple System Atrophy are located predominantly in oligodendrocytes and are rich in a second protein, p25α. P25α plays a key role in neuronal myelination by oligodendrocytes. In healthy oligodendrocytes, there is little to no α-synuclein present. If aberrant α-synuclein is present, p25α leaves the myelin sheaths and quickly co-aggregates with α-synuclein, resulting in the disruption of the cellular process and ultimately cell death. Herein, we report that p25α is susceptible for 20S proteasome-mediated degradation and that p25α induces α-synuclein aggregation, resulting in proteasome impairment and cell death. In addition, we identified small molecules 20S proteasome enhancers that prevent p25α induced α-synuclein fibrilization, restore proteasome impairment, and enhance cell viability. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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