AUTHOR=Tan Kuan Teng , Cheong Kok Whye , Wong Lai Chun , Bertrand Hélène C. , Abd Karim Nurul Huda , Chong Yie Kie , Low May Lee TITLE=Metals in medicine: unlocking new avenues for neurodegenerative disease treatment JOURNAL=Frontiers in Chemical Biology VOLUME=Volume 4 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/chemical-biology/articles/10.3389/fchbi.2025.1696058 DOI=10.3389/fchbi.2025.1696058 ISSN=2813-530X ABSTRACT=Neurodegenerative diseases (NDD) such as Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) urgently demand novel therapeutics beyond symptomatic relief. Increasing evidence implicates dysregulation of metal ion homeostasis (e.g., iron, copper, zinc) in the pathogenesis of these diseases, contributing to oxidative stress and protein aggregation. Conventional therapies face limitations including poor brain bioavailability and inability to halt disease progression. In response, metal-based strategies are emerging as promising interventions. This mini-review highlights how restoring metal ion balance and leveraging inorganic chemistry can counter neurodegeneration. We discuss recent advances in metal complexes that target pathogenic pathways, metal-organic frameworks (MOFs) as sophisticated drug delivery scaffolds, and metallic nanoparticles engineered to cross the blood-brain barrier (BBB). These approaches offer unique capabilities to modulate disease processes and deliver multi-functional treatments. By exploring the roles of metal ions in neurobiology and surveying cutting-edge metal-containing therapeutics, we underscore the potential of metals in medicine to unlock new avenues for treating NDD.