We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Oxidative Stress and Mitochondrial Complex I Dysfunction Correlate with Neurodegeneration in an α-Synucleinopathy Animal Model.
- Authors
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.
- Abstract
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.
- Subjects
OXIDATIVE stress; PEROXISOME proliferator-activated receptors; PARKINSON'S disease; NEURODEGENERATION; MITOCHONDRIA; SCRAPIE
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 19, p11394
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms231911394