Transition metal ions and neurotransmitters: coordination chemistry and implications for neurodegeneration

Neurodegeneration is characterized by a disturbance in neurotransmitter-mediated signaling pathways. Recent studies have highlighted the significant role of transition metal ions, including Cu(i/ii), Zn(ii), and Fe(ii/iii), in neurotransmission, thereby making the coordination chemistry of neurotransmitters a growing field of interest in understanding signal dysfunction. This review outlines the physiological functions of transition metal ions and neurotransmitters, with the metal-binding properties of small molecule-based neurotransmitters and neuropeptides. Additionally, we discuss the structural and conformational changes of neurotransmitters induced by redox-active metal ions, such as Cu(i/ii) and Fe(ii/iii), and briefly describe the outcomes arising from their oxidation, polymerization, and aggregation. These observations have important implications for neurodegeneration and emphasize the need for further research to develop potential therapeutic strategies.