CEXS-UPF: Peroxinitrite in the brain promotes the development of alzheimer's

CEXS-UPF: Peroxinitrite in the brain promotes the development of alzheimer's

News from CEXS-UPF

A study led by Francisco José Muñoz sheds light on the accumulation of beta-amyloid protein aggregates (Aβ) in the brain, discovering that the presence of peroxynitrite in the extracellular environment promotes the formation and stabilization of oligomeric beta-amyloid aggregates.

Oligomers and beta-amyloid fibers induce nitro oxidative stress, triggering the production of nitric oxide and free radicals in the extracellular environment. When they combine, peroxynitrite is produced, a highly reactive molecule that can modify proteins and alter their function. The study reveals that when peroxynitrite reacts with beta-amyloid oligomers, it facilitates its stabilization and prevents the formation of mature fibers. Thus, the more beta-amyloid protein there is, the more peroxynitrite formation is promoted and the latter, in turn, makes the beta-amyloid oligomers to remain stabilized, perpetuating the characteristic neuronal damage of Alzheimer's disease.

"The study of the mechanisms underlying beta-amyloid aggregation is crucial for the development of new therapeutic strategies", says Muñoz. In addition to describing the effects of nitration on beta-amyloid oligomers, the scientific team in collaboration with researchers Baldomero Oliva and David Andreu has developed a computational model according to which a mutation of the addition of the nitro group to the beta-amyloid protein stabilizes the highly toxic oligomers and prevents the formation of mature fibers. 

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Reference work: Guivernau B, Bonet J, Valls-Comamala V, Bosch-Morató M, Godoy JA, Inestrosa NC, Perálvarez-Marín A, Fernández-Busquets X, Andreu D, Oliva B, Muñoz FJ. Amyloid-β Peptide Nitrotyrosination Stabilizes Oligomers and Enhances NMDAR-Mediated Toxicity. J Neurosci. 2016 Nov 16;36(46):11693-11703. PubMed PMID: 27852777