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Table 1 Pharmacological approaches to target microglial inflammation in mouse models of tauopathy

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
Giannopoulos (2018) [108] 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