Publication: AUTOPHAGY-MEDIATED NEUROTOXIC EFFECT OF SALSOLINOL ON NE-4C NEURAL STEM CELLS
Date
2025
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Publisher
IMU University
Abstract
Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterised by the progressive loss of dopaminergic neurons in the substantia nigra. Current therapies for PD focus only on symptomatic relief and do not halt disease progression. Therefore, neural stem cell transplant has emerged as a promising cell therapy option for PD, as it has the potential to restore dopaminergic neurons. However, the survival of transplanted neural stem cells within the diseased brain remains a major challenge. Salsolinol (SAL), an endogenous and exogenous neurotoxin, has been associated with PD due to its ability to generate oxidative stress and disrupt mitochondrial function in dopaminergic neurons. However, limited research has explored its impact on neural stem cells (NSCs) and the role of autophagy in mediating this toxicity. This study investigates whether SAL exerts toxic effects on NE-4C neural stem cells through autophagy-related mechanisms. NE-4C cells were exposed to different concentrations of SAL for 24, 48, and 72 hours. Cell viability was assessed using the MTT assay to determine the IC25, IC50 and IC75. Acridine orange staining was used to detect acidic vesicle formation, indicative of autophagic activity. Expression levels of autophagy-related proteins (Atg12, Beclin-1, and LC3 A/B) were measured using cell-based ELISA. Exposure to SAL resulted in a significant, time- and dose-dependent reduction in cell viability. A significant increase in acidic vesicle formation was observed after SAL treatment, suggesting enhanced autophagic activity. Additionally, ELISA results showed elevated expression of Atg12 and Beclin-1, and significant upregulation of LC3 A/B, supporting the activation of autophagy in response to SAL treatment. These findings confirm that SAL induces autophagy-mediated neurotoxicity in NE-4C NSCs, providing insights into how endogenous neurotoxins may compromise stem cell viability in PD and suggest that regulating autophagy may help improve survival of endogenous and transplanted NSCs in PD patients.
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Keywords
Parkinson Disease, Autophagy, Neural Stem Cells, Neurotoxins, Cell Survival, Salsoline