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Oxidative Stress and Mitochondrial Complex I Dysfunction Correlate with Neurodegeneration in an α-Synucleinopathy Animal Model.

Adriana Morales-MartínezPaola A Martínez-GómezDaniel Martinez-FongMarcos M Villegas-RojasFrancisca Pérez-SeverianoMiguel A Del Toro-ColínKaren M Delgado-MinjaresVíctor Manuel Blanco-AlvarezBertha Alicia Leon-ChavezOmar Emiliano Aparicio-TrejoMauricio T Baéz-CortésMaria-Del-Carmen Cardenas-AguayoJose Luna-MuñozMar Pacheco-HerreroQuetzalli Denisse Angeles-LópezIrma A Martínez-DávilaCitlaltepetl Salinas-LaraJosé Pablo Romero-LópezCarlos Sánchez-GaribayAdolfo R Méndez-CruzLuis O Soto-Rojas
Published in: International journal of molecular sciences (2022)
The α-synucleinopathies constitute a subset of neurodegenerative disorders, of which Parkinson's disease (PD) is the most common worldwide, characterized by the accumulation of misfolded α-synuclein in the cytoplasm of neurons, which spreads in a prion-like manner to anatomically interconnected brain areas. However, it is not clear how α-synucleinopathy triggers neurodegeneration. We recently developed a rat model through a single intranigral administration of the neurotoxic β-sitosterol β-D-glucoside (BSSG), which produces α-synucleinopathy. In this model, we aimed to evaluate the temporal pattern of levels in oxidative and nitrosative stress and mitochondrial complex I (CI) dysfunction and how these biochemical parameters are associated with neurodegeneration in different brain areas with α-synucleinopathy ( Substantia nigra pars compacta , the striatum, in the hippocampus and the olfactory bulb, where α-syn aggregation spreads). Interestingly, an increase in oxidative stress and mitochondrial CI dysfunction accompanied neurodegeneration in those brain regions. Furthermore, in silico analysis suggests a high-affinity binding site for BSSG with peroxisome proliferator-activated receptors (PPAR) alpha (PPAR-α) and gamma (PPAR-γ). These findings will contribute to elucidating the pathophysiological mechanisms associated with α-synucleinopathies and lead to the identification of new early biomarkers and therapeutic targets.
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