Effect of hydrogen sulfide on alpha-synuclein aggregation and cell viability
Abstract Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder characterized by nigrostriatal degeneration and aggregation of α-synuclein (α-Syn) with accumulation of insoluble aggregates in Lewy bodies. Familial mutations in α-Syn are associated with the development of PD. A...
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Nature Portfolio
2025-05-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-99794-z |
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| author | Elena A. Ostrakhovitch Eun-Suk Song Johannah E. Stegemann Michael McLeod Tritia R. Yamasaki |
| author_facet | Elena A. Ostrakhovitch Eun-Suk Song Johannah E. Stegemann Michael McLeod Tritia R. Yamasaki |
| author_sort | Elena A. Ostrakhovitch |
| collection | DOAJ |
| description | Abstract Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder characterized by nigrostriatal degeneration and aggregation of α-synuclein (α-Syn) with accumulation of insoluble aggregates in Lewy bodies. Familial mutations in α-Syn are associated with the development of PD. Accumulation of insoluble aggregates results in neuronal toxicity. Identification of compounds that inhibit seeding activity of α-Syn is of great importance. Here we investigate the potential of H2S donor, sodium hydrosulfide (NaHS), to inhibit α-Syn aggregation. We examined the effect of NaHS on fibril growth kinetics and the structural change of α-Syn fibrils formed by self-seeding and cross-seeding of wild-type (wt) and PD familial α-Syn mutations. NaHS slowed both self- and cross-seeded A53T α-Syn fibril formation but not wild-type fibril formation. We observed a decrease in the formed fibril length in vitro. We examined the effect on fibril formation within cells. NaHS significantly reduced the number and filament length of formed oligomers in an α-Syn overexpressing cell model. Furthermore, NaHS rescued viability of A53T α-Syn overexpressing cells seeded with wt- and mutant preformed fibrils. These results support a conformation-specific effect of hydrogen sulfide on alpha-synuclein aggregation and cell viability which deserves further exploration for therapeutic potential. |
| format | Article |
| id | doaj-art-c4f12da4d2d548c99207979109ca0b5b |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-c4f12da4d2d548c99207979109ca0b5b2025-08-20T03:53:12ZengNature PortfolioScientific Reports2045-23222025-05-0115111410.1038/s41598-025-99794-zEffect of hydrogen sulfide on alpha-synuclein aggregation and cell viabilityElena A. Ostrakhovitch0Eun-Suk Song1Johannah E. Stegemann2Michael McLeod3Tritia R. Yamasaki4Department of Neurology, University of KentuckyDepartment of Neurology, University of KentuckyDepartment of Neurology, University of KentuckyDepartment of Neurology, University of KentuckyDepartment of Neurology, University of KentuckyAbstract Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder characterized by nigrostriatal degeneration and aggregation of α-synuclein (α-Syn) with accumulation of insoluble aggregates in Lewy bodies. Familial mutations in α-Syn are associated with the development of PD. Accumulation of insoluble aggregates results in neuronal toxicity. Identification of compounds that inhibit seeding activity of α-Syn is of great importance. Here we investigate the potential of H2S donor, sodium hydrosulfide (NaHS), to inhibit α-Syn aggregation. We examined the effect of NaHS on fibril growth kinetics and the structural change of α-Syn fibrils formed by self-seeding and cross-seeding of wild-type (wt) and PD familial α-Syn mutations. NaHS slowed both self- and cross-seeded A53T α-Syn fibril formation but not wild-type fibril formation. We observed a decrease in the formed fibril length in vitro. We examined the effect on fibril formation within cells. NaHS significantly reduced the number and filament length of formed oligomers in an α-Syn overexpressing cell model. Furthermore, NaHS rescued viability of A53T α-Syn overexpressing cells seeded with wt- and mutant preformed fibrils. These results support a conformation-specific effect of hydrogen sulfide on alpha-synuclein aggregation and cell viability which deserves further exploration for therapeutic potential.https://doi.org/10.1038/s41598-025-99794-zα-SynucleinParkinson diseaseProtein aggregationHydrogen sulfide |
| spellingShingle | Elena A. Ostrakhovitch Eun-Suk Song Johannah E. Stegemann Michael McLeod Tritia R. Yamasaki Effect of hydrogen sulfide on alpha-synuclein aggregation and cell viability Scientific Reports α-Synuclein Parkinson disease Protein aggregation Hydrogen sulfide |
| title | Effect of hydrogen sulfide on alpha-synuclein aggregation and cell viability |
| title_full | Effect of hydrogen sulfide on alpha-synuclein aggregation and cell viability |
| title_fullStr | Effect of hydrogen sulfide on alpha-synuclein aggregation and cell viability |
| title_full_unstemmed | Effect of hydrogen sulfide on alpha-synuclein aggregation and cell viability |
| title_short | Effect of hydrogen sulfide on alpha-synuclein aggregation and cell viability |
| title_sort | effect of hydrogen sulfide on alpha synuclein aggregation and cell viability |
| topic | α-Synuclein Parkinson disease Protein aggregation Hydrogen sulfide |
| url | https://doi.org/10.1038/s41598-025-99794-z |
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