| Autor: |
Naohito Ito, Mayumi Tsuji, Naoki Adachi, Shiro Nakamura, Avijite Kumer Sarkar, Kensuke Ikenaka, César Aguirre, Atsushi Michael Kimura, Yuji Kiuchi, Hideki Mochizuki, David B. Teplow, Kenjiro Ono |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
npj Parkinson's Disease, Vol 9, Iss 1, Pp 1-10 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2373-8057 |
| DOI: |
10.1038/s41531-023-00583-0 |
| Popis: |
Abstract α-Synuclein (αS), the causative protein of Parkinson’s disease and other α-synucleinopathies, aggregates from a low molecular weight form (LMW-αS) to a high molecular weight αS oligomer (HMW-αSo). Aggregated αS accumulates intracellularly, induces intrinsic apoptosis, is released extracellularly, and appears to propagate disease through prion-like spreading. Whether extracellular αS aggregates are cytotoxic, damage cell wall, or induce cell death is unclear. We investigated cytotoxicity and cell death caused by HMW-αSo or LMW-αS. Extracellular HMW-αSo was more cytotoxic than LMW-αS and was a crucial factor for inducing plasma membrane damage and cell death. HMW-αSo induced reactive oxygen species production and phospholipid peroxidation in the membrane, thereby impairing calcium homeostasis and disrupting plasma membrane integrity. HMW-αSo also induced extrinsic apoptosis and cell death by activating acidic sphingomyelinase. Thus, as extracellular HMW-αSo causes neuronal injury and death via cellular transmission and direct plasma membrane damage, we propose an additional disease progression pathway for α-synucleinopathies. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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