Human Molecular Chaperone Hsp60 and Its Apical Domain Suppress Amyloid Fibril Formation of α-Synuclein.

Autor: Yamamoto H; Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Tottori 680-8552, Japan., Fukui N; Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Tottori 680-8552, Japan., Adachi M; Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Koyama-Minami, Tottori 680-8552, Japan., Saiki E; Department of Chemistry and Biotechnology, Faculty of Engineering, Tottori University, Koyama-Minami, Tottori 680-8552, Japan., Yamasaki A; Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Koyama-Minami, Tottori 680-8552, Japan., Matsumura R; Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Koyama-Minami, Tottori 680-8552, Japan., Kuroyanagi D; Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Tottori 680-8552, Japan., Hongo K; Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Tottori 680-8552, Japan.; Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Koyama-Minami, Tottori 680-8552, Japan.; Department of Chemistry and Biotechnology, Faculty of Engineering, Tottori University, Koyama-Minami, Tottori 680-8552, Japan.; Center for Research on Green Sustainable Chemistry, Koyama-Minami, Tottori University, Tottori 680-8552, Japan., Mizobata T; Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Tottori 680-8552, Japan.; Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Koyama-Minami, Tottori 680-8552, Japan.; Department of Chemistry and Biotechnology, Faculty of Engineering, Tottori University, Koyama-Minami, Tottori 680-8552, Japan.; Center for Research on Green Sustainable Chemistry, Koyama-Minami, Tottori University, Tottori 680-8552, Japan., Kawata Y; Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Tottori 680-8552, Japan.; Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Koyama-Minami, Tottori 680-8552, Japan.; Department of Chemistry and Biotechnology, Faculty of Engineering, Tottori University, Koyama-Minami, Tottori 680-8552, Japan.; Center for Research on Green Sustainable Chemistry, Koyama-Minami, Tottori University, Tottori 680-8552, Japan.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2019 Dec 19; Vol. 21 (1). Date of Electronic Publication: 2019 Dec 19.
DOI: 10.3390/ijms21010047
Abstrakt: Heat shock proteins play roles in assisting other proteins to fold correctly and in preventing the aggregation and accumulation of proteins in misfolded conformations. However, the process of aging significantly degrades this ability to maintain protein homeostasis. Consequently, proteins with incorrect conformations are prone to aggregate and accumulate in cells, and this aberrant aggregation of misfolded proteins may trigger various neurodegenerative diseases, such as Parkinson's disease. Here, we investigated the possibilities of suppressing α-synuclein aggregation by using a mutant form of human chaperonin Hsp60, and a derivative of the isolated apical domain of Hsp60 (Hsp60 AD(Cys)). In vitro measurements were used to detect the effects of chaperonin on amyloid fibril formation, and interactions between Hsp60 proteins and α-synuclein were probed by quartz crystal microbalance analysis. The ability of Hsp60 AD(Cys) to suppress α-synuclein intracellular aggregation and cytotoxicity was also demonstrated. We show that Hsp60 mutant and Hsp60 AD(Cys) both effectively suppress α-synuclein amyloid fibril formation, and also demonstrate for the first time the ability of Hsp60 AD(Cys) to function as a mini-chaperone inside cells. These results highlight the possibility of using Hsp60 AD as a method of prevention and treatment of neurodegenerative diseases.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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