The Role of Complement in Synaptic Pruning and Neurodegeneration

• Main Authors: Gomez-Arboledas A, Acharya MM, Tenner AJ
• Format: Article
• Language: English
• Published: Dove Medical Press 2021-09-01
• Series: ImmunoTargets and Therapy
• Subjects: microglia; c1q; synapses; phagocytosis; inflammation.
• Online Access: https://www.dovepress.com/the-role-of-complement-in-synaptic-pruning-and-neurodegeneration-peer-reviewed-fulltext-article-ITT

Angela Gomez-Arboledas,1 Munjal M Acharya,2,3 Andrea J Tenner1,4,5 1Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA; 2Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA; 3Department of Radiation Oncology, University of California, Irvine, Irvine, CA, USA; 4Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA; 5Department of Pathology and Laboratory Medicine, University of California, Irvine, School of Medicine, Irvine, CA, USACorrespondence: Andrea J TennerDepartment of Molecular Biology and Biochemistry, University of California Irvine, 3205 McGaugh Hall, Irvine, CA, 92697, USATel [phone]Email [e-mail]: The complement system, an essential part of the innate immune system, is composed of a group of secreted and membrane proteins that collectively participate in maintaining the function of the healthy and diseased brain. However, an inappropriate activation of the complement system has been related to an inflammatory response in multiple diseases, such as stroke, traumatic brain injury, multiple sclerosis, and Alzheimer’s disease, as well as Zika infection and radiotherapy. In addition, C1q and C3 (initial activation components of the complement cascade) have been shown to play a key beneficial role in the refinement of synaptic circuits during developmental stages and adult plasticity. Nevertheless, excessive synaptic pruning in the adult brain can be detrimental and has been associated with synaptic loss in several pathological conditions. In this brief review, we will discuss the role of the complement system in synaptic pruning as well as its contribution to neurodegeneration and cognitive deficits. We also mention potential therapeutic approaches to target the complement system to treat several neuroinflammatory diseases and unintended consequences of radiotherapy.Keywords: microglia, C1q, synapses, phagocytosis, inflammation