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Updated: Apr 28, 2026
Primary Culture of Mouse Dopaminergic Neurons
Published on: September 8, 2014
A Comprehensive Review of Melatonin as Multi-Pathway Neuroprotectant Against Methamphetamine-Induced Programmed Cell
Noel Pabalan1, Sarawut Lapmanee1, Phuntila Tharabenjasin1
1Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Cooperative Learning Center, Piyachart 2, 99 Moo 18 Klong Luang, Rangsit, Pathumthani 12120, Thailand.
Introduction:
Methamphetamine (METH) abuse affects 34 million individuals globally, causing severe neurotoxicity through multiple programmed cell death (PCD) pathways. No approved pharmacotherapies exist. We comprehensively examined melatonin's neuroprotective mechanisms against METH-induced apoptosis, pyroptosis, necroptosis, and ferroptosis.
Methods:
A comprehensive review of preclinical studies examining METH neurotoxicity mechanisms and melatonin's protective effects across all PCD pathways.
Results:
METH activates apoptosis, pyroptosis, necroptosis, and ferroptosis via distinct molecular pathways. Melatonin inhibits all pathways through antioxidant, mitochondrial, anti-inflammatory, and direct signaling effects. A circadian-ferroptosis axis was identified, linking circadian disruption to ferroptosis.
Conclusions:
Melatonin exhibits strong multi-target neuroprotection and represents a promising candidate for clinical translation.
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