Oxidative stress and mitochondrial complex I dysfunction correlate with neurodegeneration in an -synucleinopathy animal model
Fecha
2022-09-27Autor
Morales-Martínez, Adriana
Martínez-Gómez, Paola A.
Martinez-Fong, Daniel
Villegas-Rojas, Marcos M.
Pérez-Severiano, Francisca
Del Toro-Colín, Miguel A.
Delgado-Minjares, Karen M.
Blanco-Alvarez, Víctor Manuel
Leon-Chavez, Bertha Alicia
Aparicio-Trejo, Omar Emiliano
Baéz-Cortés, Mauricio T.
Cardenas-Aguayo, Maria-del-Carmen
Luna-Muñoz, José
Pacheco-Herrero, Mar
Angeles-López, Quetzalli D.
Martínez-Dávila, Irma A.
Salinas-Lara, Citlaltepetl
Romero-López, José Pablo
Sánchez-Garibay, Carlos
Méndez-Cruz, Adolfo R.
Soto-Rojas, Luis O.
Metadatos
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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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