Neuroinflammation-Driven Neurodegeneration in Chronic Infections: From Mechanisms to Interventions

Neuroscience research increasingly recognizes the pivotal role of neuroinflammation in the pathogenesis of neurodegenerative diseases, particularly in the context of chronic infections. Neuroinflammation refers to sustained activation of the central nervous system’s innate immune components—primarily microglia, astrocytes, and associated cytokine networks—while neurodegeneration encompasses the progressive structural and functional loss of neurons, synapses, and neural circuits. Persistent pathogens such as viruses, bacteria, and parasites can trigger sustained immune responses in the central nervous system (CNS), leading to lasting inflammation and progressive neuronal loss. Recent studies highlight the complexity of interactions between infectious agents, resident immune cells like microglia and astrocytes, and the broader neural environment, indicating that chronic infections may be significant but underappreciated contributors to neurodegenerative disorders. These disease include, but are not limited to, Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), multiple sclerosis (MS), HIV-associated neurocognitive disorders, neurosyphilis, and tuberculous meningitis.Despite mounting evidence, the precise molecular and cellular pathways linking chronic infection, sustained neuroinflammation, and eventual neurodegeneration remain incompletely understood. Ongoing debates address the specificity versus generality of pathogen-induced neuroinflammation mechanisms, the role of comorbid factors, and the variability across diverse infections and host backgrounds. Notable advances—including findings on microbial toxins, persistent viral reservoirs, and dysregulated host immune responses—have begun to clarify possible mechanisms and therapeutic targets. However, a critical gap persists in translating this knowledge into effective interventions and preventative strategies, highlighting the need for further investigation.This Research Topic aims to dissect the intricate mechanisms linking chronic infections to neuroinflammation and the resulting neurodegenerative processes. It seeks to clarify both shared and distinct pathways across various infectious agents, investigate the contributions of innate and adaptive immunity, and evaluate the potential of emerging biomarkers and innovative therapeutics. Importantly, this Topic distinguishes between primarily neurodegenerative diseases (e.g., AD, PD, ALS, FTD), where neuroinflammation may act as an accelerant or modifier, and primarily infectious diseases (e.g., HIV, neurosyphilis, chronic viral encephalitides), where pathogen persistence is a direct driver of CNS immune activation and subsequent neurodegeneration. This separation underscores the need to understand how underlying mechanisms differ across disease categories, including the roles of pathogen burden, immune dysregulation, host genetics, and environmental cofactors. Authors are encouraged to address pressing questions, such as how pathogen persistence shapes immune responses in the CNS, which molecular pathways initiate and sustain neuroinflammation, and how targeted interventions might alter disease progression or prevent neurodegeneration altogether.To gather further insights in this interdisciplinary field spanning neuropathology, immunology, and infectious disease, we welcome articles addressing, but not limited to, the following themes:• Molecular and cellular mechanisms linking chronic infections to neuroinflammation• Pathogen-specific effects on CNS immune cell activation and signaling• The role of the blood-brain barrier and neurovascular unit in infection-induced neurodegeneration• Identification and validation of biomarkers for early detection and monitoring• Preclinical and clinical strategies for therapeutic intervention, including anti-inflammatory, antimicrobial, and neuroprotective approaches• The impact of genetic, environmental, and lifestyle factors on susceptibility and progression Topic editors: Stefania Mondello, Firas H Kobeissy Source: https://www.frontiersin.org/research-topics/77131/neuroinflammation-driven-neurodegeneration-in-chronic-infections-from-mechanisms-to-interventions