60995 20231116120807.0 doi 10.3390/ijms18030478 sideral 98582 ART-2017-98582 eng Pujols, J. High-throughput screening methodology to identify alpha-synuclein aggregation inhibitors 2017 Access copy available to the general public Unrestricted 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. info:eu-repo/grantAgreement/ES/DGA/B89 info:eu-repo/grantAgreement/ES/MICINN/BFU2013-44763-P info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064-P info:eu-repo/grantAgreement/EUR/SUDOE/INTERREG/NEUROMED-SOE4-P1-E831 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 3.687 2017 BIOCHEMISTRY & MOLECULAR BIOLOGY 90 / 292 = 0.308 2017 Q2 T1 CHEMISTRY, MULTIDISCIPLINARY 52 / 169 = 0.308 2017 Q2 T1 1.26 2017 Medicine (miscellaneous) 2017 Q1 Physical and Theoretical Chemistry 2017 Q1 Computer Science Applications 2017 Q1 Inorganic Chemistry 2017 Q1 Spectroscopy 2017 Q1 Organic Chemistry 2017 Q1 Molecular Biology 2017 Q2 Catalysis 2017 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Peña-Díaz, S. Conde-Giménez, M. Universidad de Zaragoza (orcid)0000-0003-4358-9110 Pinheiro, F. Navarro, S. Sancho, J. Universidad de Zaragoza (orcid)0000-0002-2879-9200 Ventura, S. 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 18, 3 (2017), 478 [12 pp.] Int. j. mol. sci. International Journal of Molecular Sciences 1661-6596 8190038 http://zaguan.unizar.es/record/60995/files/texto_completo.pdf Versión publicada 108535 http://zaguan.unizar.es/record/60995/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:60995 articulos driver 2023-11-16-12:00:10 ARTICLE