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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