C5 encodes the complement component 5, a critical protein in the complement system. C5 is cleaved into C5a (anaphylatoxin) and C5b, initiating the terminal complement pathway and membrane attack complex (MAC) formation. C5 plays a dual role in immune defense and inflammatory responses, with significant implications for neuroinflammation and neurodegenerative diseases.
The C5 gene encodes a component of the complement system, part of the innate immune system involved in inflammation and immune response.
Gene SymbolC5
Full NameComplement Component 5
Chromosomal Location9q33.2
Ensembl IDENSG00000102755
Associated DiseasesAge-Related Macular Degeneration, Huntington's Disease, Complement Deficiency
The C5 gene encodes complement component 5, a critical protein in the complement system. C5 is synthesized as a single polypeptide chain and is proteolytically cleaved into two functional fragments:
- C5a: A potent anaphylatoxin and pro-inflammatory mediator
- C5b: The initiating fragment for formation of the membrane attack complex (MAC)
C5 is activated by the C5 convertase (C4b2a3b in the classical pathway, C3bBbC3b in the alternative pathway). Once cleaved, C5a acts as a powerful chemoattractant for neutrophils, monocytes, and other immune cells, while C5b sequentially recruits C6, C7, C8, and C9 to form the MAC.
- Alzheimer's Disease: C5a receptors are upregulated in AD brain, and C5a contributes to neuroinflammation and microglial activation. C5a/C5aR1 signaling promotes amyloid-beta induced inflammation.
- Parkinson's Disease: C5a is implicated in neuroinflammation in the substantia nigra and contributes to dopaminergic neuron degeneration.
- Huntington's Disease: Elevated C5a levels have been observed in HD models and may contribute to disease progression.
- Amyotrophic Lateral Sclerosis: Complement activation, including C5, is involved in the inflammatory response in ALS.
- Age-Related Macular Degeneration: Genetic variants in the C5 gene are associated with AMD risk.
- C5a receptor antagonists are being investigated as potential therapies for neuroinflammatory conditions.
- Eculizumab and ravulizumab (C5 inhibitors) are used for complement-mediated diseases and may have potential in neurodegenerative conditions.
C5 is expressed in various tissues:
- Brain: Synthesized by neurons, astrocytes, and microglia. C5a receptors (C5AR1, C5AR2) are expressed in the brain.
- Liver: Primary site of complement protein synthesis
- Immune cells: Macrophages, neutrophils, monocytes
- Woodruff et al., The role of complement in neurodegenerative disease (2011)
- Pasinetti et al., Role of complement in Alzheimer's disease (2012)
- Brenner et al., C5a receptor signaling in neurodegenerative diseases (2013)