Characterisation of Amyloid Aggregation and Inhibition by Diffusion-Based Single-Molecule Fluorescence Techniques

Polanco, David (Universidad de Zaragoza) ; Carrancho, Alejandra (Universidad de Zaragoza) ; Gracia, Pablo ; Cremades, Nunilo (Universidad de Zaragoza)

Resumen: Protein amyloid aggregation has been associated with more than 50 human disorders, including the most common neurodegenerative disorders Alzheimer’s and Parkinson’s disease. Interfering with this process is considered as a promising therapeutic strategy for these diseases. Our understanding of the process of amyloid aggregation and its role in disease has typically been limited by the use of ensemble-based biochemical and biophysical techniques, owing to the intrinsic heterogeneity and complexity of the process. Single-molecule techniques, and particularly diffusion-based single-molecule fluorescence approaches, have been instrumental to obtain meaningful information on the dynamic nature of the fibril-forming process, as well as the characterisation of the heterogeneity of the amyloid aggregates and the understanding of the molecular basis of inhibition of a number of molecules with therapeutic interest. In this article, we reviewed some recent contributions on the characterisation of the amyloid aggregation process, the identification of distinct structural groups of aggregates in homotypic or heterotypic aggregation, as well as on the study of the interaction of amyloid aggregates with other molecules, allowing the estimation of the binding sites, affinities, and avidities as examples of the type of relevant information we can obtain about these processes using these techniques.

Idioma: Inglés

DOI: 10.3390/biophysica2040043

Año: 2022

Publicado en: Biophysica 2, 4 (2022), 506-524
ISSN: 2673-4125

Financiación: info:eu-repo/grantAgreement/ES/DGA/B49-20D
Financiación: info:eu-repo/grantAgreement/ES/DGA/LMP175_21
Financiación: info:eu-repo/grantAgreement/ES/FEDER/Una manera de hacer Europa
Financiación: info:eu-repo/grantAgreement/ES/MICINN-AEI/PGC2018-096335-B100
Financiación: info:eu-repo/grantAgreement/ES/MCIN/AEI/10.13039/501100011033

Tipo y forma: Review (Published version)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)