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Resumen: An increasing number of neurodegenerative diseases are being found to be associated with the abnormal accumulation of aggregated proteins in the brain. In Parkinson’s disease, this process involves the aggregation of alpha-synuclein (a-syn) into intraneuronal inclusions. Thus, compounds that inhibit a-syn aggregation represent a promising therapeutic strategy as disease-modifying agents for neurodegeneration. The formation of a-syn amyloid aggregates can be reproduced in vitro by incubation of the recombinant protein. However, the in vitro aggregation of a-syn is exceedingly slow and highly irreproducible, therefore precluding fast high throughput anti-aggregation drug screening. Here, we present a simple and easy-to-implement in-plate method for screening large chemical libraries in the search for a-syn aggregation modulators. It allows us to monitor aggregation kinetics with high reproducibility, while being faster and requiring lower protein amounts than conventional aggregation assays. We illustrate how the approach enables the identification of strong aggregation inhibitors in a library of more than 14, 000 compounds.
Idioma: Inglés
DOI: 10.3390/ijms18030478
Año: 2017
Publicado en: International Journal of Molecular Sciences 18, 3 (2017), 478 [12 pp.]
ISSN: 1661-6596
Factor impacto JCR: 3.687 (2017)
Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 90 / 292 = 0.308 (2017) - Q2 - T1
Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 52 / 169 = 0.308 (2017) - Q2 - T1
Factor impacto SCIMAGO: 1.26 - Medicine (miscellaneous) (Q1) - Physical and Theoretical Chemistry (Q1) - Computer Science Applications (Q1) - Inorganic Chemistry (Q1) - Spectroscopy (Q1) - Organic Chemistry (Q1) - Molecular Biology (Q2) - Catalysis (Q2)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B89
Financiación: info:eu-repo/grantAgreement/ES/MICINN/BFU2013-44763-P
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064-P
Financiación: info:eu-repo/grantAgreement/EUR/SUDOE/INTERREG/NEUROMED-SOE4-P1-E831
Tipo y forma: Artículo (Versión definitiva)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)

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