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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1478013
This article is part of the Research Topic Zebrafish: Bona Fide Pathophysiological Models of Human Diseases View all 7 articles

Metallothionein II treatment mitigates rotenone-induced neurodegeneration in zebrafish models of Parkinson's disease

Provisionally accepted
Yong Hui Nies Yong Hui Nies 1Wei Ling Lim Wei Ling Lim 2NORWAHIDAH ABDUL KARIM NORWAHIDAH ABDUL KARIM 3Mohamad Fairuz Yahaya Mohamad Fairuz Yahaya 1Seong Lin Teoh Seong Lin Teoh 1*
  • 1 Department of Anatomy, Faculty of medicine, Universiti Kebangsaan Malaysia, Cheras, Malaysia
  • 2 Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Kuala Lumpur, Malaysia
  • 3 Department of Biochemistry, Faculty of medicine, Universiti Kebangsaan Malaysia, Cheras, Malaysia

The final, formatted version of the article will be published soon.

    Parkinson's disease (PD) is a common neurodegenerative disorder primarily affecting motor function due to progressive loss of dopaminergic neurons in the substantia nigra. Current therapies offer symptomatic relief but fail to halt disease progression, highlighting the need for novel therapeutic strategies. This study explores the neuroprotective potential of exogenous human metallothionein 2 (hMT2) peptide in a rotenone-induced PD zebrafish model. Adult zebrafish were divided into four groups: control, rotenone-treated, hMT2 pre-treatment, and hMT2 co-treatment. PD model was established by exposing zebrafish to 5 µg/L rotenone water for 28 days. hMT2 (0.2 μg) was administered intracranially either one day before or seven days after rotenone exposure. The novel tank test demonstrated that rotenone exposure significantly impaired locomotor activity (p < 0.05) and increased anxiety-like behavior (p < 0.001). Additionally, PD model zebrafish exhibited reduced dopamine levels, decreased dopaminergic neuron population, elevated oxidative stress, heightened inflammatory response and mitochondrial dysfunction. Treatment with hMT2, especially in the co-treatment group, ameliorated these deficits by restoring locomotor activity, dopamine levels, and dopaminergic neuron counts while reducing oxidative stress and inflammation, and improving mitochondrial function. These results suggest that hMT2 holds promise as a therapeutic agent for PD.

    Keywords: neurodegenerative disease, Neuroprotection, pesticide, dopaminergic neuron, Mitochondrial function

    Received: 08 Aug 2024; Accepted: 09 Jan 2025.

    Copyright: © 2025 Nies, Lim, ABDUL KARIM, Yahaya and Teoh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Seong Lin Teoh, Department of Anatomy, Faculty of medicine, Universiti Kebangsaan Malaysia, Cheras, Malaysia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.