Objective: This study aims to investigate the role of HMGB1 protein in mediating neuroinflammatory-induced parkinsonian movement disorder of the MPTP-induced zebrafish model of Parkinson’s disease (PD).

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s and is affecting approximately 10 million people worldwide. Concerning this, the HMGB1 protein has been shown to mediate the neuroinflammatory response, which is a major contributor to the pathophysiology of Parkinson’s disease (PD). Although ample studies have investigated the effect of HMGB1 on chronic neuroinflammation, the functional role and mechanism of action of this protein in mediating neuroinflammatory-induced PD pathogenesis is still elusive. Over the decades, zebrafish have been an excellent model of neurodegenerative diseases. Additionally, the zebrafish HMGB1 protein is homologous to humans. Hence, research question on whether the parkinsonian movement disorder exhibited by zebrafish due to the induction of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin can be alleviated by inhibiting the expression of HMGB1 protein is reasonable to be put as major discussion.

Method: We investigate the role of HMGB1 in mediating neuroinflammatory response of MPTP-induced zebrafish model of PD using the knockdown method, where the expression of HMGB1 protein is suppressed by the anti-sense morpholino oligonucleotides. Behavioral test as well as molecular analyses (RT-qPCR, western blotting, and immunohistochemistry) are performed to compare the behaviors and neuroinflammatory-related gene and protein expressions between normal and HMGB1-deficient MPTP-induced zebrafish.

Results: By suppressing the expression of HMGB1 protein, MPTP-induced neuroinflammatory response is alleviated and motor symptoms of parkinsonian zebrafish is improved.

Conclusion: Our study answers the question pertaining to the involvement of HMGB1 in PD development and whether the knockdown of this protein can improve PD symptoms in zebrafish, particularly MPTP-induced movement disorders. Findings from this study could pave a way in designing potential therapies targeting molecular docking for the inhibition of HMGB1 protein. In longer term, this study will help in addressing fundamental role of HMGB1 that may open the venue for proper treatment of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-role-imposed-by-the-high-mobility-group-box-1-hmgb1-protein-in-mptp-induced-zebrafish-model-of-parkinsons-disease/