Neurotransmitter Systems in Neurodegeneration: Mechanisms, Circuits, and Therapeutic Modulation

Neurodegenerative diseases are characterized not only by progressive neuronal loss but also by early and sustained alterations in neurotransmission that critically shape disease onset, progression, and symptomatology. Converging evidence indicates that distinct yet partially overlapping patterns of dysfunction across dopaminergic, cholinergic, glutamatergic, GABAergic, and serotonergic systems are observed in major disorders such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis.These alterations arise from cell-type-specific vulnerability and network-level disturbances, linking synaptic dysfunction with neuroinflammation, oxidative stress, and protein aggregation, and in many cases precede overt neurodegeneration. Neurotransmitter imbalance is not merely a downstream consequence but an active contributor to neuronal injury through mechanisms such as excitotoxicity, calcium dysregulation, and impaired neuromodulatory control of circuit activity. Importantly, most currently approved symptomatic therapies target neurotransmitter systems, underscoring their translational relevance, while emerging approaches aim to modulate synaptic function to alter disease trajectories.This Research Topic aims to gather original research and reviews addressing the role of neurotransmitter systems in neurodegeneration across molecular, cellular, circuit, and systems-level analyses. Topics of interest include, but are not limited to:o Mechanisms of neurotransmitter dysregulationo Synaptic and network dysfunctiono Interactions with proteinopathies and neuroinflammationo Development of biomarkers based on neurotransmissiono Therapeutic strategies targeting neuromodulatory systemsWe welcome the following article types: Original Research, Review, Mini-Review, Brief Research Report, Methods, Hypothesis & Theory, and Perspective. In line with the Neurodegeneration section’s remit, submissions should clarify the underlying neurological or neurodegenerative mechanism of action and ideally include in vivo preclinical models or patient-derived cellular systems. Clinical reports, stroke studies, and general cell-death studies in cell models without disease-relevant context are out of scope.By integrating findings across disciplines, this collection seeks to advance a mechanistic understanding of how altered neurotransmission contributes to neurodegenerative processes and to identify novel avenues for intervention. Topic editors: Pablo Galeano, Eduardo Blanco Calvo Source: https://www.frontiersin.org/research-topics/81510/neurotransmitter-systems-in-neurodegeneration-mechanisms-circuits-and-therapeutic-modulation