Metabolic Peptides and Amyloidogenic Factors in Brain Function and Neurological Disease

Metabolically active peptides and hormone-derived proteins are increasingly recognized as important modulators of central nervous system function. Molecules such as islet amyloid polypeptide (IAPP, amylin), insulin and insulin-related peptides, amyloidogenic hormone fragments, and other metabolism-linked signaling factors extend far beyond their classical peripheral roles to influence neuronal excitability, synaptic transmission, cellular stress responses, and neuroinflammatory signaling. In rodents, many of these peptides interact directly with neuronal membranes, synaptic receptors, and intracellular signaling cascades, placing them at a critical interface between systemic metabolic state, brain homeostasis, and vulnerability to neurological disease.Growing evidence also indicates that metabolic peptides and amyloidogenic factors share common properties, including activity-dependent secretion, receptor-mediated signaling, membrane interactions, and context-dependent aggregation. These features enable them to act as physiological neuromodulators under healthy conditions, while contributing to synaptic dysfunction, inflammation, and neurodegeneration when dysregulated. Understanding how these molecules transition between adaptive and pathological roles remains a central challenge in molecular neuroscience.This Research Topic aims to bring together studies that investigate the molecular, cellular, and circuit-level roles of metabolically linked peptides and amyloidogenic factors in the nervous system, with particular emphasis on rodent models. We seek to clarify how peptide structure, aggregation state, receptor engagement, and intracellular signaling pathways shape synaptic inhibition, neuronal resilience or vulnerability, and disease-relevant phenotypes.We welcome submissions utilizing biochemical, genetic, electrophysiological, imaging, and pharmacological approaches, including in vivo rodent models, ex vivo brain preparations, and cellular systems. Contributions that connect metabolic peptide signaling to changes in neuronal activity, network organization, behavior, or disease progression are especially encouraged.Topics of interest include, but are not limited to:• Molecular structure, aggregation dynamics, and post-translational modification of IAPP and related metabolic peptides in neural contexts• Interactions between metabolically linked peptides, neuronal membranes, ion channels, and synaptic receptors• Modulation of inhibitory and excitatory transmission by insulin-related peptides and amyloidogenic factors• Cross-talk between metabolic signaling pathways, insulin sensitivity, and neuronal energy homeostasis• Roles of metabolic peptides in Alzheimer’s disease, diabetes-associated cognitive dysfunction, and vascular pathology• Shared mechanisms of peptide-induced cellular stress, calcium dysregulation, and neuroinflammatory activation• Circuit-level and behavioral consequences of altered peptide expression, processing, or aggregation• Comparative studies across disease models revealing convergent metabolic–neural dysfunction• Pharmacological or genetic strategies targeting peptide-related pathways to restore synaptic and metabolic balance Topic editors: Simona Daniele, Antoniette Michelle Maldonado-Devincci Source: https://www.frontiersin.org/research-topics/79613/metabolic-peptides-and-amyloidogenic-factors-in-brain-function-and-neurological-disease