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
| Â | Classical | Lectin | Alternative | C3 | Terminal (C5a, C5b-9) |
|---|---|---|---|---|---|
AD | C1q KO decreases amyloid plaques, gliosis, and hippocampal neuronal loss in Tg2576 model [91] | Â | Â | 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] | Â | Â | Â | 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] | Â | Â | 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 | Â | 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] | Â | FB KO or FB antibody results in delayed onset and reduced severity of symptoms [120] | sCR1 & CVF attenuate demyelination, disease severity [121, 122] | Â |