Mitophagy: a bridge linking HMGB1 and Parkinson’s disease using adult zebrafish as a model organism

Razali, Khairiah and Mohd Nasir, Mohd Hamzah and Kumar, Jaya and Mohamed, Wael Mohamed Yousef (2023) Mitophagy: a bridge linking HMGB1 and Parkinson’s disease using adult zebrafish as a model organism. Brain Sciences, 13 (7). pp. 1-15. E-ISSN 2076-3425

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Abstract

High-mobility group box 1 (HMGB1) has been implicated as a key player in two criticalfactors of Parkinson’s disease (PD): mitochondrial dysfunction and neuroinflammation. However, thespecific role of HMGB1 in PD remains elusive. We investigated the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration on mitochondrial dysfunction and HMGB1-associatedinflammatory genes as well as locomotor activity in zebrafish, aiming to elucidate the role of HMGB1in PD. Adult zebrafish received MPTP injections, and locomotor activity was measured at 24- and48-h post-administration. Gene expression levels related to mitophagy (fis1, pink1, and park2) andHMGB1-mediated inflammation (hmgb1, tlr4, and nfkb) were quantified through RT-qPCR analysis.Following MPTP injection, the significant increase in transcript levels of fis1, pink1, and park2 in-dicated notable changes in PINK1/Parkin mitophagy, while the upregulation of hmgb1, tlr4, andnfkb genes pointed to the activation of the HMGB1/TLR4/NFκB inflammatory pathway. Further-more, MPTP-injected zebrafish exhibited decreased locomotor activity, evident through reduceddistance travelled, mean speed, and increased freezing durations. HMGB1 plays a major role incellular processes as it is involved in both the mitophagy process and functions as a pro-inflammatoryprotein. MPTP administration in adult zebrafish activated mitophagy and inflammatory signaling,highlighting the significant role of HMGB1 as a mediator in both processes and further emphasizingits significant contribution to PD pathogenesis

Item Type:	Article (Journal)
Uncontrolled Keywords:	Parkinson’s disease; high-mobility group box 1; MPTP; mitochondrial dysfunction; neuroinflammation; zebrafish
Subjects:	R Medicine > R Medicine (General)
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Medicine Kulliyyah of Medicine > Department of Basic Medical Kulliyyah of Science Kulliyyah of Science > Department of Biotechnology
Depositing User:	Dr Wael Mohamed
Date Deposited:	18 Jul 2023 15:12
Last Modified:	18 Jul 2023 15:16
URI:	http://irep.iium.edu.my/id/eprint/105633

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