The small molecule ZPD-2 inhibits the aggregation and seeded polymerisation of C-terminally truncated a-Synuclein

Protein aggregation, particularly the formation of amyloid fibrils, is associated with numerous human disorders, including Parkinson's disease. This neurodegenerative condition is characterised by the accumulation of alpha-Synuclein amyloid fibrils within intraneuronal deposits known as Lewy bo...

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Detalles Bibliográficos
Autores: Peña-Díaz, S, Ventura, S
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Institut d'Investigació i Innovació Parc Taulí (I3PT)
Repositorio:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
OAI Identifier:oai:i3pt.fundanetsuite.com:p5310
Acceso en línea:https://i3pt.portalinvestigacion.com/publicaciones/5310
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85207786636&doi=10.1111%2ffebs.17310&partnerID=40&md5=f972a9bd9168280c7e6f17f55711cd80
Access Level:acceso abierto
Palabra clave:inhibition
oligomer
protein aggregation
truncation
alpha-Synuclein
Descripción
Sumario:Protein aggregation, particularly the formation of amyloid fibrils, is associated with numerous human disorders, including Parkinson's disease. This neurodegenerative condition is characterised by the accumulation of alpha-Synuclein amyloid fibrils within intraneuronal deposits known as Lewy bodies or neurites. C-terminally truncated forms of alpha-Synuclein are frequently observed in these inclusions in the brains of patients, and their increased aggregation propensity suggests a role in the disease's pathogenesis. This study demonstrates that the small molecule ZPD-2 acts as a potent inhibitor of both the spontaneous and seeded amyloid polimerisation of C-terminally truncated alpha-Synuclein by interfering with early aggregation intermediates. This dual activity positions this molecule as a promising candidate for therapeutic development in treating synucleinopathies.