C1q binding and complement activation by prions and amyloids.
C1q binds to many non-self and altered-self-materials. These include microorganisms, immune complexes, apoptotic and necrotic cells and their breakdown products, and amyloids. C1q binding to amyloid fibrils found as extracellular deposits in tissues, and subsequent complement activation are involved in the pathology of several amyloid diseases, such as Alzheimer's disease. Prion diseases, such as scrapie also involve formation of amyloid by polymerization of the host prion protein (PrP). Complement activation is likely to contribute to neuronal damage in the end stages of prion diseases, but is also thought to participate in the initial infection, dissemination and replication stages. Infectious prion particles are likely to bind C1q and activate the complement system. Bound complement proteins may then influence the uptake and transport of prion particles by dendritic cells (DCs) and their subsequent proliferation at sites such as follicular DCs.
Sim
Robert B
RB
MRC Immunochemistry Unit, Department of Biochemistry, Oxford University, South Parks Road, Oxford OX1 3QU, UK. bob.sim@bioch.ox.ac.uk
Kishore
Uday
U
Villiers
Christian L
CL
Marche
Patrice N
PN
Mitchell
Daniel A
DA
D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D003167:Complement Activation / Q000276:immunology*; D015922:Complement C1q / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007239:Infections / Q000378:metabolism / Q000473:pathology; D017096:Prion Diseases / Q000378:metabolism / Q000473:pathology; D011328:Prions / Q000378:metabolism*
D000682:Amyloid; D011328:Prions; D015922:Complement C1q