Amyloid-ß and a-Synuclein Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical Scavenging and Redox Silencing

Pedersen, J.T. ; Chen, S.W. ; Borg, C.B. ; Ness, S. ; Bahl, J.M. ; Heegaard, N.H.H. ; Dobson, C.M. ; Hemmingsen, L. ; Cremades, N. (Universidad de Zaragoza) ; Teilum, K.

Resumen: The formation of reactive oxygen species (ROS) is linked to the pathogenesis of neurodegenerative diseases. Here we have investigated the effect of soluble and aggregated amyloid-ß (Aß) and a-synuclein (aS), associated with Alzheimer''s and Parkinson''s diseases, respectively, on the Cu2+-catalyzed formation of ROS in vitro in the presence of a biological reductant. We find that the levels of ROS, and the rate by which ROS is generated, are significantly reduced when Cu2+ is bound to Aß or aS, particularly when they are in their oligomeric or fibrillar forms. This effect is attributed to a combination of radical scavenging and redox silencing mechanisms. Our findings suggest that the increase in ROS associated with the accumulation of aggregated Aß or aS does not result from a particularly ROS-active form of these peptides, but rather from either a local increase of Cu2+ and other ROS-active metal ions in the aggregates or as a downstream consequence of the formation of the pathological amyloid structures.

Idioma: Inglés

DOI: 10.1021/jacs.5b13577

Año: 2016

Publicado en: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 138, 12 (2016), 3966-3969
ISSN: 0002-7863

Factor impacto JCR: 13.858 (2016)

Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 10 / 166 = 0.06 (2016) - Q1 - T1

Factor impacto SCIMAGO: 7.492 - Biochemistry (Q1) - Colloid and Surface Chemistry (Q1) - Chemistry (miscellaneous) (Q1) - Catalysis (Q1)

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)