TCE-mediated neuroprotection against rotenone-induced dopaminergic neuronal death in PD mice: insights into the Nrf-2/PINK1/Parkin-mitophagy pathway

被引：0

作者：

Hagera Dilnashin ^{[1
]}

Shekhar Singh ^{[1
]}

Poonam Rawat ^{[1
]}

Aaina Singh Rathore ^{[1
]}

Richa Singh ^{[1
]}

Priyanka Kumari Keshri ^{[1
]}

Nitesh Kumar Gupta ^{[1
]}

Singh Ankit Satyaprakash ^{[1
]}

Surya Pratap Singh ^{[1
]}

机构：

[1] Department of Biochemistry, Institute of Science, Banaras Hindu University, U.P., Varanasi

来源：

Metabolic Brain Disease | / 40卷 / 4期

关键词：

Mitochondrial dysfunction; Mitophagy; Nrf-2; Oxidative stress; PINK1/Parkin; T; cordifolia;

D O I：

10.1007/s11011-025-01595-w

中图分类号：

学科分类号：

摘要：

Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of Parkinson’s disease (PD). In a previous study, we reported that an extract of T. cordifolia (TCE) possessed antioxidant and anti-apoptotic properties that improved mitochondrial function against rotenone-induced neurotoxicity. However, the underlying molecular mechanism remains unclear. In this study, we found that rotenone (ROT)-induced PD mice exhibited mitochondrial abnormalities, including defective mitophagy, mitochondrial reactive oxygen species (ROS) overexpression, and mitochondrial fragmentation, accompanied by reduced expression of Pink1 and Parkin and increased apoptosis. These changes were partially reversed following oral administration of TCE. Moreover, TCE restored the activity and translocation of NF-E2-related factor 2 (Nrf2) and upregulated the expression of antioxidant enzymes (SOD1, SOD2, GSH, and GSSH). Interestingly, ROT also activates mitophagy. Our results suggest that ROT toxicity can cause neuronal cell death through mitophagy-mediated signaling in PD mice. However, TCE reversed this activity by inhibiting autophagic protein (LC3B-II/LC3B-I) activation and increasing specific mitochondrial proteins (TOM20, Pink1, and Parkin). Our findings indicated that TCE provides neuroprotection against rotenone-induced toxicity in PD mice by stimulating endogenous antioxidant enzymes and inhibiting ROT-induced oxidative stress by potentiating the Nrf-2/Pink1/Parkin-mediated survival mechanism. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.

引用

共 63 条

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