Complement cascades and brain disorders

Jovchevska, Ivana (author), Videtič Paska, Alja (author), Kouter, Katarina (author)

The complement system is a vital component of innate immunity. Besides its roles in pathogen defense, its significance in neurodevelopment, neurodegeneration, and cancer progression is beginning to be recognized. We performed a comprehensive literature review to summarize the involvement and dysregulation of the complement system in three main CNS-associated conditions: Alzheimer's disease, schizophrenia, and glioma. In Alzheimer's disease, activation of the complement system contributes to neuroinflammation, synaptic loss, and neuronal death. In glioblastoma, complement promotes tumor growth, immune evasion, and therapy resistance. In schizophrenia, genetic variations in complement components, particularly C4A, are associated with synaptic pruning abnormalities and disease susceptibility. We conclude that the complement system has a dual role of protector and pathogenic mediator in the central nervous system. While it is critical in neurodegenerative, oncological, and psychiatric disorders, its role is not understood well enough. For therapeutic purposes, targeting the complement system may open new frontiers for therapeutic interventions without disrupting important physiological processes. More research is needed to elucidate the exact roles of the complement and help translate these findings into clinical settings.

• Language: English
• Keywords: complement system, humoral immunity, immune system, innate immunity, neurodegeneration, neurology, oncology, psychiatric disorders
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 21 str.
• Numbering: Vol. 15, iss. 8, art. 1179
• PID: 20.500.12556/RUL-178196
• UDC: 616.8
• ISSN on article: 2218-273X
• DOI: 10.3390/biom15081179
• COBISS.SI-ID: 248447747
• Publication date in RUL: 21.01.2026

Record is a part of a journal

• Title: Biomolecules
• Publisher: MDPI
• ISSN: 2218-273X
• COBISS.SI-ID: 519952921

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: sistem komplementa, homoralna imunost, imunski sistem, prirojena imunost, nevrodegeneracija, nevrologija, onkologija, psihiatrične motnje

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P1-0390
• Name: Funkcijska genomika in biotehnologija za zdravje

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P3-0083
• Name: Odnosi parazitskega obstajanja