Table 1.
Pharmacological tools for modulating microglial polarization.
| Targets | Small-molecules | Models | Effects | Reference |
|---|---|---|---|---|
| Nuclear receptors | ||||
| PPARγ (agonist) | Pioglitazone | AD mice | M1 to M2 switch, reverse cognitive deficits | Toba et al., 2016 |
| DSP-8658 | AD mice | Enhanced microglial phagocytosis, improved memory | Yamanaka et al., 2012 | |
| MDG548 | PD mice in vitro | Neuroprotection, reduction of NF-κB activation | Lecca et al., 2015 | |
| SNU-BP | LPS model | Increased M2 and decreased M1 | Song et al., 2016 | |
| RXR (agonist) | Bexarotene | AD mice and in vitro | Clearance of β-amyloid, reverse cognitive deficits | Cramer et al., 2012 |
| Metabolism-associated molecules | ||||
| AMPK (activator) | Metformin | MCAo PD mice | M2 polarization, angiogenesis, neurogenesis, improved locomotor activity | Jin et al., 2014; Patil et al., 2014 |
| PDK (inhibitor) | DCA | CFA inflammation model, in vitro | M1/M2 switch, reduced pain and inflammation | Jha et al., 2015 |
| Aldose reductase (inhibitor) | Fidarestat (SNK-860) | SCI model In vitro | M2 polarization Reduced LPS-induced inflammation | Zhang et al., 2016; Reddy et al., 2010 |
| cAMP-dependent pathway for M2 polarization | ||||
| PKA (activator) | Db-cAMP | SCI model | Induce M2 phenotype | Ghosh et al., 2016 |
| PDE4 (inhibitor) | Rolipram PDE4D-NAM | Aged mice and primates | Neuroprotective, anti-inflammatory Memory consolidation | Barad et al., 1998; Burgin et al., 2010 |
| PDE5 (inhibitor) | Sildenafil | MCAo AD mice EAE model | M1/M2 modulation Clearance of β-amyloid prevent axonal loss promote re-myelination | Puzzo et al., 2009; Pifarre et al., 2011; Moretti et al., 2016 |
| Redox signaling molecules for microglial M1/M2 balance | ||||
| NOX (inhibitor) | Apocynin | In vitro PD mice | Induce M2 polarization protect from dopaminergic neuron degeneration | Choi et al., 2012; Hernandes et al., 2013a |
| GKT137831 | Diabetic retinopathy, in vitro | Hypoxia-induced ROS production and the expression of inflammatory cytokines in retinal microglia | Deliyanti and Wilkinson-Berka, 2015 | |
| M1 polarization for inhibiting glioma cell growth | ||||
| mTOR (inhibitor) | Rad | Glioma | M1 polarization, prevented glioma growth | Lisi et al., 2014 |
| – | Chlorogenic acid | Glioma | Increased M1 and decreased M2 reduction of tumor size | Xue et al., 2017 |
| Other signaling molecules | ||||
| HDAC (inhibitor) | Scriptaid | TBI In vitro model | M2 polarization, protect white brain matter, suppress LPS-induced cytokine expression | Wang et al., 2015; Kannan et al., 2013 |
| ROCK (inhibitor) | FSD-C10 Y-39983 | EAE model EAE model | Inhibit neuroinflammation Attenuation of demyelination | Li et al., 2014; Gao et al., 2013 |
| Fasudil | In vitro | M2 polarization | Chen et al., 2014a | |
AD, Alzheimer’s disease; PD, Parkinson’s disease; MS, multiple sclerosis; MCAo, middle cerebral artery occlusion; SCI, spinal cord injury; TBI, traumatic brain injury; EAE, experimental allergic encephalomyelitis; CFA, complete Freund’s adjuvant; LPS, lipopolysaccharide; PDE4D-NAM, PDE4D negative allosteric modulator.