As a Potential Therapeutic Target, C1q Induces Synapse Loss Via Inflammasome-activating Apoptotic and Mitochondria Impairment Mechanisms in Alzheimer's Disease

Overview

Journal J Neuroimmune Pharmacol

Specialties Allergy & Immunology
Neurology
Pharmacology

Date 2023 Jun 29

PMID 37386257

Authors

Pei-Pei Guan

Tong-Qi Ge

Pu Wang

Affiliations

Soon will be listed here.

Abstract

C1q, the initiator of the classical pathway of the complement system, is activated during Alzheimer's disease (AD) development and progression and is especially associated with the production and deposition of β-amyloid protein (Aβ) and phosphorylated tau in β-amyloid plaques (APs) and neurofibrillary tangles (NFTs). Activation of C1q is responsible for induction of synapse loss, leading to neurodegeneration in AD. Mechanistically, C1q could activate glial cells, which results in the loss of synapses via regulation of synapse pruning and phagocytosis in AD. In addition, C1q induces neuroinflammation by inducing proinflammatory cytokine secretion, which is partially mediated by inflammasome activation. Activation of inflammasomes might mediate the effects of C1q on induction of synapse apoptosis. On the other hand, activation of C1q impairs mitochondria, which hinders the renovation and regeneration of synapses. All these actions of C1q contribute to the loss of synapses during neurodegeneration in AD. Therefore, pharmacological, or genetic interventions targeting C1q may provide potential therapeutic strategies for combating AD.

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