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

2022; Multidisciplinary Digital Publishing Institute; Volume: 23; Issue: 19 Linguagem: Inglês

10.3390/ijms231911394

1661-6596

Adriana Morales-Martínez, Paola A. Martínez-Gómez, Daniel Martínez‐Fong, Marcos M. Villegas-Rojas, Francisca Pérez‐Severiano, Miguel A. Del Toro-Colín, Karen M. Delgado-Minjares, Víctor Manuel Blanco-Álvarez, Bertha Alicia León‐Chávez, Omar Emiliano Aparicio‐Trejo, Mauricio T. Baéz-Cortés, María del Carmen Cárdenas‐Aguayo, José Luna‐Muñoz, Mar Pacheco‐Herrero, Quetzalli D. Angeles-López, Irma A. Martínez‐Dávila, Citlaltépetl Salinas-Lara, José Pablo Romero‐López, Carlos Sánchez-Garibay, Adolfo René Méndez‐Cruz, Luis O. Soto-Rojas,

Biochemical Acid Research Studies

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.