High-throughput screening methodology to identify alpha-synuclein aggregation inhibitors
Pujols Pujol, Jordi (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Peña Díaz, Samuel (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Conde Giménez, María (Universidad de Zaragoza. Instituto Universitario de Investigación de Biocomputación y Física de Sistemas Complejos)
Pinheiro, Francisca (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Navarro, Susanna (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Sancho, Javier (Universidad de Zaragoza. Instituto Universitario de Investigación de Biocomputación y Física de Sistemas Complejos)
Ventura, Salvador (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Date:	2017
Abstract:	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 (α-syn) into intraneuronal inclusions. Thus, compounds that inhibit α-syn aggregation represent a promising therapeutic strategy as disease-modifying agents for neurodegeneration. The formation of α-syn amyloid aggregates can be reproduced in vitro by incubation of the recombinant protein. However, the in vitro aggregation of α-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 α-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.
Grants:	Ministerio de Economía y Competitividad BFU2013-47064-P Ministerio de Economía y Competitividad BFU2013-44763-P
Note:	Salvador Ventura and Javier Sancho are supported by SOE4/P1/E831 grant from SUDOE. INTERREG IV B. EUROPEAN UNION.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	High-throughput screening ; α-synuclein ; Parkinson disease ; Amyloid ; Protein aggregation
Published in:	International journal of molecular sciences, Vol. 18 (March 2017) , art. 478, ISSN 1422-0067

DOI: 10.3390/ijms18030478
PMID: 28257086

12 p, 12.3 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles