000060995 001__ 60995
000060995 005__ 20231116120807.0
000060995 0247_ $$2doi$$a10.3390/ijms18030478
000060995 0248_ $$2sideral$$a98582
000060995 037__ $$aART-2017-98582
000060995 041__ $$aeng
000060995 100__ $$aPujols, J.
000060995 245__ $$aHigh-throughput screening methodology to identify alpha-synuclein aggregation inhibitors
000060995 260__ $$c2017
000060995 5060_ $$aAccess copy available to the general public$$fUnrestricted
000060995 5203_ $$aAn 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.
000060995 536__ $$9info:eu-repo/grantAgreement/EUR/SUDOE/INTERREG/NEUROMED-SOE4-P1-E831$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064-P$$9info:eu-repo/grantAgreement/ES/MICINN/BFU2013-44763-P$$9info:eu-repo/grantAgreement/ES/DGA/B89
000060995 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000060995 590__ $$a3.687$$b2017
000060995 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b90 / 292 = 0.308$$c2017$$dQ2$$eT1
000060995 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b52 / 169 = 0.308$$c2017$$dQ2$$eT1
000060995 592__ $$a1.26$$b2017
000060995 593__ $$aMedicine (miscellaneous)$$c2017$$dQ1
000060995 593__ $$aPhysical and Theoretical Chemistry$$c2017$$dQ1
000060995 593__ $$aComputer Science Applications$$c2017$$dQ1
000060995 593__ $$aInorganic Chemistry$$c2017$$dQ1
000060995 593__ $$aSpectroscopy$$c2017$$dQ1
000060995 593__ $$aOrganic Chemistry$$c2017$$dQ1
000060995 593__ $$aMolecular Biology$$c2017$$dQ2
000060995 593__ $$aCatalysis$$c2017$$dQ2
000060995 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000060995 700__ $$aPeña-Díaz, S.
000060995 700__ $$0(orcid)0000-0003-4358-9110$$aConde-Giménez, M.$$uUniversidad de Zaragoza
000060995 700__ $$aPinheiro, F.
000060995 700__ $$aNavarro, S.
000060995 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, J.$$uUniversidad de Zaragoza
000060995 700__ $$aVentura, S.
000060995 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000060995 773__ $$g18, 3 (2017), 478 [12 pp.]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000060995 8564_ $$s8190038$$uhttps://zaguan.unizar.es/record/60995/files/texto_completo.pdf$$yVersión publicada
000060995 8564_ $$s108535$$uhttps://zaguan.unizar.es/record/60995/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000060995 909CO $$ooai:zaguan.unizar.es:60995$$particulos$$pdriver
000060995 951__ $$a2023-11-16-12:00:10
000060995 980__ $$aARTICLE