[Advances in multi-omics research on methamphetamine-induced neurotoxicity and addiction]

Methamphetamine (METH) is highly addictive and can cause neurotoxicity when misused over a prolonged period. METH-induced neurotoxicity and addiction involve multi-level biological alterations, including nucleotide polymorphisms, aberrant epigenetic modifications, transcriptional imbalance, protein dysfunction, metabolic dysregulation, and microbial dysbiosis with changes in microbiota-derived metabolites. To systematically dissect these multifaceted changes, genomics has been deployed to identify key gene polymorphisms linked to METH addiction susceptibility and epigenetic changes such as DNA methylation in brain regions following METH exposure. Tran-scriptomics dynamically profiles differential gene expression in addiction-relevant brain areas, particularly in pathways governing synaptic plasticity and neuroinflammation. Proteomics pinpoints the dysregulation of functional proteins associated with synaptic plasticity in response to METH. Metabolomics quantifies neurotransmitter depletion and redox imbalance induced by the drug, while microbiomics reveals gut microbiota dysbiosis and subsequent neural damage via the gut-brain axis. The integrated application of these multi-omics technologies-spanning genetic variation, transcriptional regulation, protein function, metabolic dynamics, and host-microbe interactions-systematically illuminates the complex molecular events underlying METH neurotoxicity and addiction, thereby providing a robust theoretical framework and technical roadmap for identifying early warning biomarkers and devising multi-target combination strategies against METH neurotoxicity and relapse. This review summarizes the current state of single-omics and multi-omics applications in METH neurotoxicity and addiction research, aiming to provide a reference for elucidating pathogenic mechanisms, identifying biomarkers, and discovering potential therapeutic targets.