Complement 3a induces the synapse loss via C3aR in mitochondria-dependent NLRP3 activating mechanisms during the development and progression of Alzheimer's disease.
Neurosci Biobehav Rev
; 165: 105868, 2024 Oct.
Article
em En
| MEDLINE
| ID: mdl-39218048
ABSTRACT
As a central molecule in complement system (CS), complement (C) 3 is upregulated in the patients and animal models of Alzheimer's disease (AD). C3 will metabolize to iC3b and C3a. iC3b is responsible for clearing ß-amyloid protein (Aß). In this scenario, C3 exerts neuroprotective effects against the disease via iC3b. However, C3a will inhibit microglia to clear the Aß, leading to the deposition of Aß and impair the functions of synapses. To their effects on AD, activation of C3a and C3a receptor (C3aR) will impair the mitochondria, leading to the release of reactive oxygen species (ROS), which activates the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasomes. The overloading of NLRP3 inflammasomes activate microglia, leading to the formation of inflammatory environment. The inflammatory environment will facilitate the deposition of Aß and abnormal synapse pruning, which results in the progression of AD. Therefore, the current review will decipher the mechanisms of C3a inducing the synapse loss via C3aR in mitochondria-dependent NLRP3 activating mechanisms, which facilitates the understanding the AD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Receptores de Complemento
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Complemento C3a
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Doença de Alzheimer
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Proteína 3 que Contém Domínio de Pirina da Família NLR
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Mitocôndrias
Limite:
Animals
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Humans
Idioma:
En
Revista:
Neurosci Biobehav Rev
Ano de publicação:
2024
Tipo de documento:
Article