en Toxicology Toxicology Experimental research article Experimental research article <p><span style="font-size:12px;"><span style="font-family:Arial;"><span style="line-height:150%"><b><span lang="EN-US"><span style="line-height:150%"><span new="" roman="" times="">Background</span></span></span></b><span lang="EN-US"><span style="line-height:150%"><span new="" roman="" times=""> 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. </span></span></span></span><br /> <span style="line-height:150%"><b><span lang="EN-US"><span style="line-height:150%"><span new="" roman="" times="">Methods</span></span></span></b><span lang="EN-US"><span style="line-height:150%"><span new="" roman="" times=""> 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. </span></span></span></span><br /> <span style="line-height:150%"><b><span lang="EN-US"><span style="line-height:150%"><span new="" roman="" times="">Results</span></span></span></b><span lang="EN-US"><span style="line-height:150%"><span new="" roman="" times=""> Results reveal 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. </span></span></span></span><br /> <span style="line-height:150%"><b><span lang="EN-US"><span style="line-height:150%"><span new="" roman="" times="">Conclusion</span></span></span></b><span lang="EN-US"><span style="line-height:150%"><span new="" roman="" times=""> Our findings suggest that salsolinol induces mitophagy <i>via</i> the PINK1/PARKIN-mediated mitophagy and receptor-mediated mitophagy pathways.</span></span></span></span></span></span></p> Parkinson's disease,Salsolinol,Mitophagy,PINK1,PARKIN 0 0 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 3200319475328460038058 3200319475328460038058 No UNSW Chooi Ling Lim chooi_linglim@imu.edu.my 3200319475328460038059 3200319475328460038059 No IMU University Yong Qi Leong yong.leong@monash.edu 3200319475328460038060 3200319475328460038060 No Monash University Malaysia Soi Moi Chye chye_soimoi@imu.edu.my 3200319475328460038061 3200319475328460038061 No IMU University Yin Yin Ooi YinYin.Ooi@taylors.edu.my 3200319475328460038062 3200319475328460038062 No IMU University Anna Pick Kiong Ling anna_ling@imu.edu.my 3200319475328460038063 3200319475328460038063 No IMU University Kenny Gah Leong Voon Kenny.Voon@nottingham.edu.my 3200319475328460038064 3200319475328460038064 No University of Nottingham Rhun Yian Koh rhunyian_koh@imu.edu.my 3200319475328460038065 3200319475328460038065 Yes IMU University