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Modulation of Alzheimer's Disease Aß40 Fibril Polymorphism by the Small Heat Shock Protein αB-Crystallin.
Rodina, Natalia; Hornung, Simon; Sarkar, Riddhiman; Suladze, Saba; Peters, Carsten; Schmid, Philipp W N; Niu, Zheng; Haslbeck, Martin; Buchner, Johannes; Kapurniotu, Aphrodite; Reif, Bernd.
Afiliação
  • Rodina N; Helmholtz-Zentrum München (HMGU), Deutsches Forschungszentrum für Gesundheit und Umwelt, Institute of Structural Biology (STB), Ingolstädter Landstr. 1, Neuherberg 85764, Germany.
  • Hornung S; Division of Peptide Biochemistry, TUM School of Life Sciences, Technical University of Munich, Emil-Erlenmeyer-Forum 5, Freising 85354, Germany.
  • Sarkar R; Helmholtz-Zentrum München (HMGU), Deutsches Forschungszentrum für Gesundheit und Umwelt, Institute of Structural Biology (STB), Ingolstädter Landstr. 1, Neuherberg 85764, Germany.
  • Niu Z; School of Pharmacy, Henan University, Kaifeng, Henan 475004, China.
  • Kapurniotu A; Division of Peptide Biochemistry, TUM School of Life Sciences, Technical University of Munich, Emil-Erlenmeyer-Forum 5, Freising 85354, Germany.
  • Reif B; Helmholtz-Zentrum München (HMGU), Deutsches Forschungszentrum für Gesundheit und Umwelt, Institute of Structural Biology (STB), Ingolstädter Landstr. 1, Neuherberg 85764, Germany.
J Am Chem Soc ; 146(28): 19077-19087, 2024 Jul 17.
Article em En | MEDLINE | ID: mdl-38973199
ABSTRACT
Deposition of amyloid plaques in the brains of Alzheimer's disease (AD) patients is a hallmark of the disease. AD plaques consist primarily of the beta-amyloid (Aß) peptide but can contain other factors such as lipids, proteoglycans, and chaperones. So far, it is unclear how the cellular environment modulates fibril polymorphism and how differences in fibril structure affect cell viability. The small heat-shock protein (sHSP) alpha-B-Crystallin (αBC) is abundant in brains of AD patients, and colocalizes with Aß amyloid plaques. Using solid-state NMR spectroscopy, we show that the Aß40 fibril seed structure is not replicated in the presence of the sHSP. αBC prevents the generation of a compact fibril structure and leads to the formation of a new polymorph with a dynamic N-terminus. We find that the N-terminal fuzzy coat and the stability of the C-terminal residues in the Aß40 fibril core affect the chemical and thermodynamic stability of the fibrils and influence their seeding capacity. We believe that our results yield a better understanding of how sHSP, such as αBC, that are part of the cellular environment, can affect fibril structures related to cell degeneration in amyloid diseases.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos beta-Amiloides / Cadeia B de alfa-Cristalina / Doença de Alzheimer Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos beta-Amiloides / Cadeia B de alfa-Cristalina / Doença de Alzheimer Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article