Integrating Neuroinflammation and Metabolomics to Decode Neurodegenerative Diseases: Mechanisms and Targeted Interventions, Volume II

This Research Topic is part of the Integrating Neuroinflammation and Metabolomics to Decode Neurodegenerative Diseases: Mechanisms and Targeted Interventions series: Integrating Neuroinflammation and Metabolomics to Decode Neurodegenerative Diseases Mechanisms and Targeted Interventions.Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, and related disorders, represent a major and growing global health challenge. Despite advances in genetics, neuropathology, multi-omics, and disease modeling, the mechanisms that initiate and sustain disease progression remain incompletely understood, and truly disease-modifying therapies remain limited. Increasing evidence indicates that neurodegeneration is influenced not only by processes within the central nervous system but also by communication between the brain and peripheral organs. The gut–brain and heart–brain axes may regulate neuroimmune activity, metabolism, vascular function, blood–brain barrier integrity, and neuronal resilience, yet the mechanisms and clinical relevance of these interactions remain insufficiently defined.Neurodegeneration is driven not by isolated pathways but by persistent neuroimmune and metabolic coupling across cellular ecosystems. Chronic activation of microglia and astrocytes reshapes cytokine networks, synaptic function, and blood-brain barrier homeostasis, while neurons and glia undergo coordinated shifts in bioenergetics, lipid turnover, mitochondrial function, and redox control. Metabolomics and lipidomics are uniquely positioned to quantify these dynamic states in biofluids, tissue, and model systems, thereby linking molecular mechanisms to clinically measurable phenotypes. Yet inflammation and metabolism are still often investigated separately, which weakens causal inference, limits cross-cohort reproducibility, and slows the development of patient-stratified therapies. This Research Topic is designed to close the translational gap between mechanistic discovery and clinical application by integrating neuroinflammation with metabolomics across neurodegenerative disorders. We aim to build a coherent framework that links immune signaling, metabolic remodeling, and disease heterogeneity across molecular, cellular, circuit, and clinical scales. By emphasizing cross-platform reproducibility and biologically interpretable models, the Topic seeks to advance both mechanistic understanding and therapeutic development. We particularly encourage studies that combine metabolomic and lipidomic profiling with imaging, genetics, proteomics, and deeply phenotyped longitudinal cohorts.Topics of interest include, but are not limited to:• Gut–brain and heart–brain axis mechanisms: microbiome-derived metabolites, lipid mediators, cardiovascular, vascular, autonomic, endocrine, and systemic inflammatory signals influencing brain health and neurodegeneration.• Neuroimmune and metabolic crosstalk: immune-driven metabolic rewiring, microglial and astrocytic responses, mitochondrial dysfunction, redox imbalance, and altered lipid metabolism across the central nervous system and peripheral organs.• Inter-organ regulation of the neurovascular unit: blood–brain barrier dysfunction, vascular inflammation, endothelial signaling, and the effects of cardiovascular and peripheral vascular disease on neuronal and glial function.• Multi-omics, biomarkers, and disease phenotyping: CSF, blood, tissue, microbiome, metabolomic, lipidomic, proteomic, genetic, imaging, and longitudinal clinical data for diagnosis, prognosis, risk stratification, and treatment-response monitoring.• Mechanistic and translational models: causal studies and experimental models of brain–peripheral organ communication, including cellular systems, animal models, organoids, patient-derived models, and integrated computational approaches.• Clinical implications and therapeutic opportunities: inter-organ mechanisms underlying cognitive, motor, behavioral, and neuropsychiatric symptoms, alongside immunometabolic, microbiome-based, cardiovascular, and other axis-modulating interventions. Topic editors: Jinming Han, Jianwei Shi, Ruiqing Ni, Keying Zhu, Jing Wu Source: https://www.frontiersin.org/research-topics/84255/integrating-neuroinflammation-and-metabolomics-to-decode-neurodegenerative-diseases-mechanisms-and-targeted-interventions-volume-ii