Volume 30, Issue 2 (June 2026)
Physiol Pharmacol 2026, 30(2): 227-241 |
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Zhang S H, Lim C L, Leong Y Q, Chye S M, Ooi Y Y, Ling A P K, et al . Salsolinol toxicity in SH-SY5Y cells: PINK1/
PARKIN and receptor-mediated mitophagy. Physiol Pharmacol 2026; 30 (2) :227-241
URL: http://ppj.phypha.ir/article-1-2538-en.html
URL: http://ppj.phypha.ir/article-1-2538-en.html
Shi Hong Zhang 
, Chooi Ling Lim , Yong Qi Leong , Soi Moi Chye , Yin Yin Ooi , Anna Pick Kiong Ling , Kenny Gah Leong Voon , Rhun Yian Koh 
, Chooi Ling Lim , Yong Qi Leong , Soi Moi Chye , Yin Yin Ooi , Anna Pick Kiong Ling , Kenny Gah Leong Voon , Rhun Yian Koh
Abstract: (990 Views)
Introduction: Parkinson’s disease (PD) is commonly characterised by motor movement deterioration and cognitive impairment. Salsolinol, a dopamine-derived endogenous neurotoxin, may contribute to PD pathogenesis due to its structural and chemical similarity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the precise molecular mechanisms of the neurotoxin remain unexplored. Hence, this study aimed to evaluate the toxic effects of salsolinol on SH-SY5Y neuronal cells, focusing on mitophagy and its associated pathways.
Methods: SH-SY5Y cells were exposed to salsolinol for toxicity assessment using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and inhibitory concentrations (ICs) were determined for the following assays. Induction of autophagy and mitophagy in the salsolinol-treated SH-SY5Y cells was detected with acridine orange and Mtphagy Dye, respectively. Additionally, an enzyme-linked immunosorbent assay (ELISA) was performed to determine the protein levels of the PINK1/PARKIN-mediated mitophagy pathway and the receptor-mediated mitophagy pathway in salsolinol-treated SH-SY5Y cells.
Results: Results revealed that SH-SY5Y cells, when treated with salsolinol (0 to 400 μM) for 24 and 48 hours, significantly elicited dose-dependent neurotoxicity. The upregulation of autophagy and mitophagy coincided with increased levels of proteins related to the PINK1/PARKIN-mediated mitophagy pathway and the receptor-mediated mitophagy pathway when treated with IC50 and IC75 as compared to untreated (UT) and IC25.
Conclusion: Our findings suggest that salsolinol induces mitophagy via the PINK1/PARKIN-mediated mitophagy and receptor-mediated mitophagy pathways.
Type of Manuscript: Experimental research article |
Subject:
Toxicology
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