Methamphetamine-Driven Neuroinflammation and Parkinson's Disease Pathology: Mechanistic Insight into Nrf2 and NFĸB...

Methamphetamine (METH) abuse has emerged as a significant public health concern due to its widespread use and persistent adverse effects on brain function. Accumulating evidence indicates that chronic METH exposure disrupts dopaminergic neurotransmission and induces neurotoxic processes that overlap with key pathological features of Parkinson's disease (PD). This review critically examines clinical, epidemiological, and experimental studies exploring the association between METH use and increased vulnerability to PD-related neurodegeneration. Particular emphasis is placed on findings from animal models and cellular studies demonstrating dopamine depletion, motor impairments, mitochondrial dysfunction, and sustained neuroinflammatory responses following METH exposure. The review highlights oxidative stress and neuroinflammation as central mechanisms linking METH-induced neurotoxicity to PD pathology. Emerging evidence suggests that METH-driven activation of the NFĸB promotes the release of proinflammatory cytokines, thereby exacerbating neuronal injury, while concurrent impairment of Nrf2 signaling compromises antioxidant defense and cellular resilience. Dysregulation and crosstalk between the NFĸB and Nrf2 pathways appear to play a critical role in sustaining chronic inflammation, redox imbalance, and progressive dopaminergic neuronal loss. By integrating molecular, cellular, and translational evidence, this review provides mechanistic insights into the contribution of Nrf2 and NFĸB signaling pathways to METH-associated neuroinflammation and PD-related pathology. Furthermore, it discusses the therapeutic potential of targeting these pathways and underscores the need for longitudinal studies to clarify causality. Finally, the review addresses broader public health implications, emphasizing the importance of preventive strategies, awareness programs, and future research aimed at mitigating the long-term consequences of methamphetamine abuse.