Skip to main content

Table 2 Therapeutic potential of inhibition/deletion of Complement components in models of neurodegenerative diseases

From: The good, the bad, and the opportunities of the complement system in neurodegenerative disease

  Classical Lectin Alternative C3 Terminal (C5a, C5b-9)
AD C1q KO decreases amyloid plaques, gliosis, and hippocampal neuronal loss in Tg2576 model [91]    C3 KO attenuates synaptic loss, gliosis, cognitive decline in APP/PS1 model [92] C5aR1 KO attenuates cognitive decline, promotes microglial clearance, protects neuronal integrity in Arctic model [93]. PMX205 reduces plaque load, cognitive loss in Tg2576/3xTg [94]
ALS Deletion of C1q or C4 does not alter disease onset or severity suggesting classical pathway is not essential [82, 95]     PMX205, C5aR1 KO, C6 ASO in SODG93A mice delays progression, extends survival, improves motor function [82, 96, 97, 98, 99]
Stroke C1q KO [100], C1qsiRNA [101], C1inh [102] reduces infarct volume, promotes neurogenesis, protects BBB MBL KO mice have improved neurological scores, reduced infarct volume, reduced C4 deposition [103, 104] FB KO, CR2-fH treatment improved neurological scores, reduced infarct volume after MCAO [105] C3 KO [106], B4Crry treatment [107] reduces infarct volume, inflammation, improves neurological function C6 KO is not protective in MCAO and CD59a KO does not reduce damage, suggesting terminal complement pathway is not essential for MCAO injury [105]
Epilepsy C1q KO increases hyperexcitability and risk of spontaneous seizures [62, 108]    Intravenous immunoglobulins (IVIg) blocks C3 & reduces spontaneous seizures after SE [109] C5 KO mice have fewer seizures [110], PMX53 reduces seizure length, probability of subsequent seizure in kainite model [111, 112]
TBI C1inh, anti-C1q Ab [113], C4KO [114] reduces lesion size, improves cognitive and motor outcomes   FB KO [115], CR2fH [116] reduces glial scarring, neuronal death, lesion size, motor and cognitive deficits C3 KO [113], CR2Crry [116] improves motor and cognitive function, reduces scarring long term. CR2-CD59 [117], C6 ASO, & OmCl [118] reduce neurological deficits, inflammation, neuronal damage short term only [116]
MS (EAE) C4 KO has no effect, suggesting classical pathway is not essential [119]   FB KO or FB antibody results in delayed onset and reduced severity of symptoms [120] sCR1 & CVF attenuate demyelination, disease severity [121, 122]