Affiliation:
1. Institut de Biotecnologia i de Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona , Bellaterra, Barcelona 08193, Spain
2. Center for Molecular Biology of Heidelberg University (ZMBH) , Heidelberg 69120, Germany
3. Clinical Research Centre, Medical University of Białystok , Kilińskiego 1, Białystok 15-369, Poland
Abstract
Abstract
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, yet effective treatments able to stop or delay disease progression remain elusive. The aggregation of a presynaptic protein, α-synuclein (aSyn), is the primary neurological hallmark of PD and, thus, a promising target for therapeutic intervention. However, the lack of consensus on the molecular properties required to specifically bind the toxic species formed during aSyn aggregation has hindered the development of therapeutic molecules. Recently, we defined and experimentally validated a peptide architecture that demonstrated high affinity and selectivity in binding to aSyn toxic oligomers and fibrils, effectively preventing aSyn pathogenic aggregation. Human peptides with such properties may have neuroprotective activities and hold a huge therapeutic interest. Driven by this idea, here, we developed a discriminative algorithm for the screening of human endogenous neuropeptides, antimicrobial peptides and diet-derived bioactive peptides with the potential to inhibit aSyn aggregation. We identified over 100 unique biogenic peptide candidates and ensembled a comprehensive database (aSynPEP-DB) that collects their physicochemical features, source datasets and additional therapeutic-relevant information, including their sites of expression and associated pathways. Besides, we provide access to the discriminative algorithm to extend its application to the screening of artificial peptides or new peptide datasets. aSynPEP-DB is a unique repository of peptides with the potential to modulate aSyn aggregation, serving as a platform for the identification of previously unexplored therapeutic agents.
Database URL: https://asynpepdb.ppmclab.com/
Funder
Consell Català de Recerca i Innovació
HORIZON EUROPE European Innovation Council
Institució Catalana de Recerca i Estudis Avançats
European Union-Next Generation EU
Ministerio de Ciencia e Innovación
Publisher
Oxford University Press (OUP)
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Information Systems