The complement system is a central component of innate immunity and plays a critical role in the central nervous system (CNS), both in normal physiology and across a wide spectrum of neurological conditions. Under homeostatic conditions (notably during brain development), complement contributes to synaptic refinement and clearance of cellular debris. In contrast, chronic or dysregulated complement activation in CNS injury or disease drives neuroinflammation, synapse loss, and neurodegeneration. These effects have been characterized across numerous conditions, including Traumatic Brain Injury (TBI), Spinal Cord Injury (SCI), Alzheimer's Disease (AD), Parkinson's Disease (PD), Stroke, Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and others. Recent advances in understanding complement's dual roles in the CNS have spurred development of targeted therapeutics, several of which are now in clinical trials, though most address rare diseases. Expanding this research to highlight the recent advances related to complement's neuroinflammatory and neuroprotective roles in neurological conditions remains essential.
This Research Topic aims to advance understanding of how complement activation shapes the neuroinflammatory landscape in CNS injury and disease. A major objective is to highlight recent findings on complement's contribution to neurological disorders, helping identify therapeutic targets and guide drug development toward clinical trials. Studies investigating specific complement pathways, dissecting the role of intracellular complement as well as local versus circulating complement, regulatory proteins, and cellular targets are of particular importance in this regard. Notably, emerging evidence also supports a neuroprotective role for complement activation, and contributions exploring this dimension are equally welcome. Recent clinical milestones (including FDA-approved complement inhibitors) have renewed urgency in this field. A growing body of evidence implicates complement in both the acute and chronic phases of CNS injury and disease. Additionally, complement has been shown to play a role in the gut-brain axis under both normal and pathological conditions, an area warranting further investigation to optimize therapeutic strategies. We invite contributions that investigate complement activation in CNS injury (TBI, SCI, Stroke) and disease states (AD, PD, ALS, MS), identify protective versus pathological roles of complement, and evaluate complement-targeted interventions in preclinical and clinical settings. Studies leveraging advanced models, including patient-derived samples, are particularly encouraged.
We welcome the following submission types: Original Research, Review, Case Report, Clinical Trial, Study Protocol, Brief Research Report, Classification, Editorial, FAIR² Data, FAIR² DATA Direct Submission, General Commentary, Hypothesis and Theory, Methods, Mini Review, Opinion, Perspective, Systematic Review, Technology and Code.
• Complement-driven neuroinflammation and neurodegeneration in AD, PD, ALS, MS, and other CNS disorders
• Complement activation in acute and chronic neurotrauma, including TBI and SCI
• Neuroprotective roles of complement in CNS injury and disorders
• Role of complement and glial cell (microglia, astrocytes) crosstalk in CNS injury and disorders
• Complement receptor expression and cell-type-specific responses in CNS injury and disorders
• Sex differences, aging, and genetic risk factors modulating complement in CNS injury and disorders
• Contribution of complement to gut-brain function in healthy and pathological CNS states
• Translational and clinical studies: biomarkers, imaging of complement activation, and new therapeutics
• Non-canonical complement functions in healthy and injured or diseased CNS
Article types and fees
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Brief Research Report
Classification
Clinical Trial
Editorial
FAIR² Data
General Commentary
Hypothesis and Theory
Methods
Mini Review
Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.
Article types
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
