Alpha-Mangostin Alleviates Mitochondrial Damage and Autophagy Dysregulation in the MPP+ Cellular Model of Parkinson’s Disease
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Issued Date
2025-01-01
Resource Type
ISSN
26334682
eISSN
26334690
Scopus ID
2-s2.0-105013677983
Journal Title
Advances in Pharmacological and Pharmaceutical Sciences
Volume
2025
Issue
1
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SCOPUS
Bibliographic Citation
Advances in Pharmacological and Pharmaceutical Sciences Vol.2025 No.1 (2025)
Suggested Citation
Abraham K.J., Dharmasaroja P. Alpha-Mangostin Alleviates Mitochondrial Damage and Autophagy Dysregulation in the MPP+ Cellular Model of Parkinson’s Disease. Advances in Pharmacological and Pharmaceutical Sciences Vol.2025 No.1 (2025). doi:10.1155/adpp/5567858 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111871
Title
Alpha-Mangostin Alleviates Mitochondrial Damage and Autophagy Dysregulation in the MPP+ Cellular Model of Parkinson’s Disease
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Abstract
Alpha-mangostin (α-M), a xanthone derivative with known antioxidative properties, has demonstrated a protective effect on neurons under oxidative stress, a key factor in the pathogenesis of Parkinson’s disease (PD). However, its impact on mitochondrial integrity and autophagy in PD remains insufficiently understood. Therefore, the present study aimed to investigate the role of α-M in regulating defective mitochondrial proteins and its influence on the mTOR pathway, both of which are critical in the regulation of autophagy. This study investigated the effects of α-M pretreatment on 1-methyl-4-phenylpyridinium (MPP<sup>+</sup>)-induced neurotoxicity in SH-SY5Y dopaminergic neurons. MPP<sup>+</sup>, a mitochondrial complex I inhibitor, significantly reduced the expression of mitochondrial proteins NDUFS3 and TIMM23, induced mitochondrial damage, and triggered excessive autophagy, as evidenced by elevated LC3-II/LC3-I ratio and phospho-Beclin-1 expression. These changes were accompanied by dysregulation of the mTOR signaling pathway, including increased phosphorylation of mTOR and suppression of its downstream effector p70S6K. α-M pretreatment restored NDUFS3 and TIMM23 levels, preserved mitochondrial morphology and membrane potential, and reduced autophagy activation by mitigating MPP<sup>+</sup>-induced LC3B accumulation and Beclin-1 activation. Additionally, α-M restored balance in the mTOR signaling pathway by reducing mTOR phosphorylation and restoring p70S6K activity, counteracting the autophagic dysregulation caused by MPP<sup>+</sup>. Importantly, α-M exhibited no toxicity under normal conditions, indicating its protective effects are context-dependent and activated only during cellular stress. These findings highlight the potential of α-M as a therapeutic agent for PD, providing neuroprotection through its targeted modulation of mitochondrial proteins and mTOR signaling that regulates autophagy.