This Research Topic focuses on the intriguing relationship between synaptic architecture and the multifaceted roles of metal ions—such as Ca²⁺, Zn²⁺, Cu²⁺, Li⁺, Pb2+ and Cd²⁺—in neuronal health and disease management. An increasing body of research over the past decade highlights the significance of metal ions in molecular neuroscience, from synaptic signaling to structural plasticity. Key findings have shown that metal ions are integral to maintaining both the functional integrity and signaling capabilities of synaptic connections and remodelling as well as causative to inducing synaptic dysfunction, even synaptic loss, due to imbalances or neurotoxic, xenobiotic metal exposure. Noteworthy advances, such as the role of Ca2+ -in modulation of synaptic palmitoylation in homeostatic synaptic downscaling and a novel mechanism underlying activity- and experience-dependent plasticity of synaptic zinc signaling, continue to push the boundaries of our understanding, particularly in modeling metal ion dynamics within synapses.
Despite these advances, several limitations persist, including unresolved questions about the exact pathways and mechanisms involved in metal ion-driven neurodevelopment, neurofunction, neuroprotection, and neurotoxicity. Insights into the delicate balance of metal ion homeostasis within neural systems remain incomplete, highlighting unexplored avenues for therapeutic interventions in neurological conditions. Addressing these gaps is essential for a deeper scientific understanding, which could lead to innovations in managing neurodegenerative diseases for therapeutic treatment and prevention, and improving cognitive health.
Goal(s)
In this Research Topic, we aim to explore key aspects of synaptic structure and metal ion roles, fostering a vibrant discussion around these themes to advance our understanding of neuronal health and pathology. Our objectives include elucidating regulatory mechanisms and discovering novel therapeutic and prevention strategies targeting metal ion dysregulation.
Scope and Information for Authors
We particularly welcome the submission of Original Research, Review, Methods, and Perspective articles on the following sub-topics:
o The role of synaptic structure in neuronal signaling and plasticity influenced by metal ions
o Mechanisms regulating synaptic integrity in health and disease
o Models for simulating metal ion dynamics under physiological and pathological conditions
o The contributions of metal ions to learning, memory, and neurodegeneration
o Therapeutic approaches to modulate metal ion signaling in neurological contexts
We invite contributions that push the boundaries of current knowledge, providing insights that could transform the understanding and management of neuronal health.

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Synaptic Architecture and the Multifaceted Roles of Metal Ions in Neuronal Health and Disease Management