Metal ion dyshomeostasis in neurological disorders: from pathological mechanisms to targeted neuroprotective and regenerative strategies.

Metal ions play an indispensable role in maintaining the physiological functions of the nervous system, while their dyshomeostasis also drives the pathogenesis of various neurological disorders. Their involvement spans from acute traumatic brain injury to chronic neurodegenerative diseases, in which they participate in pathological regulation through mechanisms such as homeostatic disruption, oxidative stress, induction of specific cell death pathways, thereby influencing secondary neuronal death and impaired regeneration. This review summarizes the pathophysiological roles of metal ions and their associations with acquired brain injury and neurodegenerative diseases, aiming to further elucidate targetable therapeutic windows for neuroprotection and neural repair. Furthermore, we evaluate the translational challenges of clinical-stage metal chelators (e.g., deferiprone, PBT2) and highlight novel nano-delivery strategies designed to cross the blood-brain barrier to reverse subcellular metal toxicity. This provides a clear therapeutic roadmap for developing next-generation neuroprotective drugs.