| Autor: |
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. |
| Předmět: |
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| Zdroj: |
International Journal of Molecular Sciences; Oct2022, Vol. 23 Issue 19, p11394, 21p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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