en Toxicology Toxicology Experimental research article Experimental research article <p style="text-align: justify;"><span style="font-size:12px;"><span style="font-family:Arial;"><strong>Introduction: </strong>Parkinson&rsquo;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.<br /> <strong>Methods:</strong> 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.&nbsp;<br /> <strong>Results:</strong> Results revealed that SH-SY5Y cells, when treated with salsolinol (0 to 400 &mu;M) 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.&nbsp;<br /> <strong>Conclusion:</strong> Our findings suggest that salsolinol induces mitophagy via the PINK1/PARKIN-mediated mitophagy and receptor-mediated mitophagy pathways.</span></span></p> Parkinson Disease, Salsolinol, Mitophagy, PINK1, PARKIN 227 241 http://ppj.phypha.ir/browse.php?a_code=A-10-2568-2&slc_lang=en&sid=1 Shi Hong Zhang 00000034540@student.imu.edu.my 3200319475328460039398 3200319475328460039398 No School of Clinical Medicine, UNSW, Sydney, New South Wales, Australia Chooi Ling Lim chooi_linglim@imu.edu.my 3200319475328460039399 3200319475328460039399 No School of Health Sciences, IMU University, Bukit Jalil, Kuala Lumpur, Malaysia Yong Qi Leong yong.leong@monash.edu 3200319475328460039400 3200319475328460039400 No School of Pharmacy, Monash University Malaysia, Subang Jaya, Selangor, Malaysia Soi Moi Chye chye_soimoi@imu.edu.my 3200319475328460039401 3200319475328460039401 No School of Health Sciences, IMU University, Bukit Jalil, Kuala Lumpur, Malaysia Yin Yin Ooi YinYin.Ooi@taylors.edu.my 3200319475328460039402 3200319475328460039402 No School of Biosciences, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya, Selangor, Malaysia Anna Pick Kiong Ling anna_ling@imu.edu.my 3200319475328460039403 3200319475328460039403 No School of Health Sciences, IMU University, Bukit Jalil, Kuala Lumpur, Malaysia Kenny Gah Leong Voon Kenny.Voon@nottingham.edu.my 3200319475328460039404 3200319475328460039404 No School of Pharmacy, University of Nottingham, Semenyih, Selangor, Malaysia Rhun Yian Koh rhunyian_koh@imu.edu.my 3200319475328460039405 0000000341908288 Yes School of Health Sciences, IMU University, Bukit Jalil, Kuala Lumpur, Malaysia