Treatment Options for Metal-associated CNS Toxicity: Clinical Trials and Translational Research

Metals are vital to human health, contributing to cellular structure, gene expression, enzymatic functions, neurotransmission, and antioxidant defense. However, dysregulation in metal homeostasis—caused by environmental, occupational, or biological factors—can lead to severe health issues, particularly neurodegenerative disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease. Essential biometals such as iron, zinc, copper, manganese, magnesium, and calcium are crucial for physiological balance, while their dysregulation is linked to oxidative stress, protein aggregation, and neurodegeneration. Toxic metals like aluminium, cadmium, lead, and mercury further exacerbate these effects by impairing immune and mitochondrial function. Research has increasingly focused on metal transport mechanisms in neurological disorders. Therapeutic interventions include chelating agents to remove excess metals and drugs targeting metal transporters to restore balance. While preclinical models show promise, challenges persist in translating findings to human therapies due to individual variability and disease complexity. Longitudinal studies emphasize the importance of tracking metal exposure over time to better understand disease progression. Preventive and therapeutic strategies also involve dietary regulation and supplementation with essential minerals, along with minimizing exposure to harmful metals, especially in occupational settings. Emerging approaches integrate multi-omics technologies—genomics, proteomics, and metabolomics—to understand the complex role of metals in disease. AI-driven diagnostics and nanomedicine further enhance precision in diagnosis and treatment. This multidisciplinary approach highlights the need for continued research and collaboration to effectively address metal dysregulation and its implications for human health.