From: Intersection of pathological tau and microglia at the synapse
Publication | Target (drug name) | Potential mechanism | Mouse line, age at start of study, administration schedule | Results |
---|---|---|---|---|
Yoshiyama (2007) [322] | Calcineurin (FK506/Tacrolimus) | Immunosuppression | PS19 (1N4R/P301S) 2M, drug in drinking water until 6M or 12M | ↓atrophy/neurodegeneration, ↓neuroinflammation, ↓ tau pathology, ↑survival |
Noble (2009) [226] | Multiple (Minocycline) | Anti-inflammatory | hTau (6 isoforms), 3-4M or 12M, 14 days, daily i.p. | ↓caspase activity, ↓truncated tau, ↓p-tau, ↓aggregated tau |
Garwood (2010) [104] | Multiple (Minocycline) | Anti-inflammatory | hTau 3-4M, 14 days daily i.p. | ↓astrogliosis, ↓pro-inflammatory cytokines |
Laurent (2017) [175] | CD3 (145-2C11) | Depletion of T-cells | THY-Tau22 (4R1N/G272V & P301S) 4M, every 2 weeks i.p. until 9M | ↓spatial memory deficits, ↓neuroinflammation, normalization of synaptic plasticity, NC tau pathology |
Asai (2015) [12] | CSF1 (PLX3397) | Depletion of microglia | PS19 3.5M, WT injected with Tau AAV, drug in food for 1M | ↓tau spreading (AAV), ↓p-tau (PS19), ↓pro-inflammatory cytokines, rescue of network hypoexcitability |
Bennett (2018) [26] | CSF1 (PLX3397) | Depletion of microglia (partial) | Tg4510 (0N4R/P301L) 12M, drug in food for 3M | NC tau pathology, NC atrophy, NC blood vessel morphology, NC astrocyte activation |
Dejanovic (2018) [75] | C1q (M1) | Inhibition complement cascade, reduction synapse phagocytosis | PS19 9M, 1x hippocampal injection | ↓synapse phagocytosis, ↓synapse loss |
Litvinchuk (2018) [190] | pSTAT3 (SH-4-54) | Inhibition of signalling downstream of C3aR | PS19 7M, 3x/week i.p. until 9M | ↓neuroinflammation, ↓tau pathology |
Bussian (2018) [47] | Bcl-2, Bcl-XL, Bcl-w (ABT263/Navitoclax) | Removal of senescent glia | PS19 weaning age, cycles of 5D daily (oral galvage) with 16D rest until 6M | ↓P-tau |
Giannopoulos (2015) [110] | 5-lipoxygenase (Zileuton) | Reduction leukotriene-induced inflammation | hTau 3M, drug 3x per week in drinking water until 10M | ↓P-tau, ↓neuroinflammation, ↓synapse loss, rescue of synaptic deficits, rescue of cognitive deficits |
5-lipoxygenase (Zileuton) | Reduction leukotriene-induced inflammation | PS19 3M, drug 3x per week in drinking water until 10M | ↓P-tau, ↓neuroinflammation, ↓synapse loss, rescue of cognitive deficits | |
Stancu (2019) [284] | NLRP3 inhibitor (MCC950) | Inflammasome inhibition | PS19 (injected with PFF) 3M, i.c.v. with osmotic pumps for 7W | ↓tau pathology, ↓microgliosis |