Complement component 8 (C8) (C8)

Complement component 8 (C8) is a heterotrimeric protein complex consisting of alpha (C8A), beta (C8B), and gamma (C8G) subunits, playing a critical role in the terminal stage of the complement cascade [1, 2]. It serves as a key assembly component of the membrane attack complex (MAC), where it binds to the C5b-7 complex and facilitates the polymerization of C9 to form cytolytic pores in target cell membranes [4, 7]. Genetically determined deficiencies in C8 subunits are strongly associated with an increased susceptibility to recurrent Neisserial infections, particularly meningococcal meningitis [11, 13]. Beyond its role in pathogen lysis, recent studies have identified C8G as a potential neuroprotective factor that antagonizes sphingosine-1-phosphate receptor 2 (S1PR2) to mitigate neuroinflammation and protect blood-brain barrier integrity in conditions like Alzheimer's disease [10, 17]. While no drugs currently target C8 directly in clinical practice, terminal pathway inhibitors like eculizumab indirectly modulate its activity by blocking upstream C5 activation [12, 18]. Research into subunit-specific modulators and recombinant C8G represents an emerging area of therapeutic interest for inflammatory and neurodegenerative disorders [1, 22].

Other names

C8AC8BC8GComplement C8Eighth component of complement

Inhibition of membrane attack complex (MAC) assembly; Antagonism of sphingosine-1-phosphate receptor 2 (S1PR2)