Methamphetamine-Induced Neurodegeneration: Role of Oxidative Stress, Neuroinflammation, Excitotoxicity and Mitochondrial Toxicity
DOI:
https://doi.org/10.65761/jbs.2026.43Keywords:
Methamphetamine; Neurodegeneration; Oxidative Stress; Neuroinflammation; Mitochondrial DysfunctionAbstract
Background: Methamphetamine (METH) is a potent psychostimulant associated with substantial neurotoxicity and progressive neuronal damage. Its neurodegenerative effects involve multiple interconnected cellular and molecular mechanisms, including oxidative stress, neuroinflammation, excitotoxicity, and mitochondrial dysfunction.
This study aimed to examine the major mechanisms underlying METH-induced neurodegeneration and summarize potential therapeutic approaches targeting these pathways
Methods: Experimental evidence concerning METH-induced alterations in dopaminergic and glutamatergic neurotransmission, reactive oxygen species (ROS) generation, microglial activation, inflammatory signaling, mitochondrial dysfunction, excitotoxicity, and apoptosis was evaluated. Evidence regarding antioxidant, anti-inflammatory, mitochondrial-protective, and glutamate-modulating interventions was also considered.
Results: METH markedly increases dopamine and glutamate release, promoting ROS generation and excitotoxic neuronal injury. Oxidative stress contributes to lipid, protein, and DNA damage, whereas microglial activation increases inflammatory cytokines, including TNF-α, IL-1β, and IL-6. METH-associated mitochondrial dysfunction further increases ROS production, decreases ATP availability, and promotes apoptotic signaling. These mechanisms interact through reinforcing feedback pathways that accelerate neuronal degeneration. Several experimental compounds, including antioxidants and glutamate-modulating agents, demonstrate neuroprotective potential.
Conclusion: METH-induced neurodegeneration results from interconnected oxidative, inflammatory, excitotoxic, and mitochondrial mechanisms. Multi-target therapeutic strategies may provide greater neuroprotection than approaches directed toward a single pathway
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