Amyloid Fragmentation and Disaggregation in Yeast and Animals
Amyloids are filamentous protein aggregates that are associated with a number of incurable diseases, termed amyloidoses. Amyloids can also manifest as infectious or heritable particles, known as prions. While just one prion is known in humans and animals, more than ten prion amyloids have been disco...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/12/1884 |
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| author | Vitaly V. Kushnirov Alexander A. Dergalev Alexander I. Alexandrov |
| author_facet | Vitaly V. Kushnirov Alexander A. Dergalev Alexander I. Alexandrov |
| author_sort | Vitaly V. Kushnirov |
| collection | DOAJ |
| description | Amyloids are filamentous protein aggregates that are associated with a number of incurable diseases, termed amyloidoses. Amyloids can also manifest as infectious or heritable particles, known as prions. While just one prion is known in humans and animals, more than ten prion amyloids have been discovered in fungi. The propagation of fungal prion amyloids requires the chaperone Hsp104, though in excess it can eliminate some prions. Even though Hsp104 acts to disassemble prion fibrils, at normal levels it fragments them into multiple smaller pieces, which ensures prion propagation and accelerates prion conversion. Animals lack Hsp104, but disaggregation is performed by the same complement of chaperones that assist Hsp104 in yeast—Hsp40, Hsp70, and Hsp110. Exogenous Hsp104 can efficiently cooperate with these chaperones in animals and promotes disaggregation, especially of large amyloid aggregates, which indicates its potential as a treatment for amyloid diseases. However, despite the significant effects, Hsp104 and its potentiated variants may be insufficient to fully dissolve amyloid. In this review, we consider chaperone mechanisms acting to disassemble heritable protein aggregates in yeast and animals, and their potential use in the therapy of human amyloid diseases. |
| first_indexed | 2024-03-10T04:32:51Z |
| format | Article |
| id | doaj.art-84869c5e218946c0b8b55f7cfd412dc7 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T04:32:51Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-84869c5e218946c0b8b55f7cfd412dc72023-11-23T04:00:41ZengMDPI AGBiomolecules2218-273X2021-12-011112188410.3390/biom11121884Amyloid Fragmentation and Disaggregation in Yeast and AnimalsVitaly V. Kushnirov0Alexander A. Dergalev1Alexander I. Alexandrov2Bach Institute of Biochemistry, Federal Research Center “Fundamentals of Biotechnology” of the Russian Academy of Sciences, 119071 Moscow, RussiaBach Institute of Biochemistry, Federal Research Center “Fundamentals of Biotechnology” of the Russian Academy of Sciences, 119071 Moscow, RussiaBach Institute of Biochemistry, Federal Research Center “Fundamentals of Biotechnology” of the Russian Academy of Sciences, 119071 Moscow, RussiaAmyloids are filamentous protein aggregates that are associated with a number of incurable diseases, termed amyloidoses. Amyloids can also manifest as infectious or heritable particles, known as prions. While just one prion is known in humans and animals, more than ten prion amyloids have been discovered in fungi. The propagation of fungal prion amyloids requires the chaperone Hsp104, though in excess it can eliminate some prions. Even though Hsp104 acts to disassemble prion fibrils, at normal levels it fragments them into multiple smaller pieces, which ensures prion propagation and accelerates prion conversion. Animals lack Hsp104, but disaggregation is performed by the same complement of chaperones that assist Hsp104 in yeast—Hsp40, Hsp70, and Hsp110. Exogenous Hsp104 can efficiently cooperate with these chaperones in animals and promotes disaggregation, especially of large amyloid aggregates, which indicates its potential as a treatment for amyloid diseases. However, despite the significant effects, Hsp104 and its potentiated variants may be insufficient to fully dissolve amyloid. In this review, we consider chaperone mechanisms acting to disassemble heritable protein aggregates in yeast and animals, and their potential use in the therapy of human amyloid diseases.https://www.mdpi.com/2218-273X/11/12/1884amyloidprionchaperoneamyloid fragmentationSup35α-synuclein |
| spellingShingle | Vitaly V. Kushnirov Alexander A. Dergalev Alexander I. Alexandrov Amyloid Fragmentation and Disaggregation in Yeast and Animals Biomolecules amyloid prion chaperone amyloid fragmentation Sup35 α-synuclein |
| title | Amyloid Fragmentation and Disaggregation in Yeast and Animals |
| title_full | Amyloid Fragmentation and Disaggregation in Yeast and Animals |
| title_fullStr | Amyloid Fragmentation and Disaggregation in Yeast and Animals |
| title_full_unstemmed | Amyloid Fragmentation and Disaggregation in Yeast and Animals |
| title_short | Amyloid Fragmentation and Disaggregation in Yeast and Animals |
| title_sort | amyloid fragmentation and disaggregation in yeast and animals |
| topic | amyloid prion chaperone amyloid fragmentation Sup35 α-synuclein |
| url | https://www.mdpi.com/2218-273X/11/12/1884 |
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