Table 1.
Preclinical approaches affecting microglia M1/M2 phenotype in transgenic mutant superoxide dismutase1 (mSOD1) mice.
| Drug administered/Genes silenced | Action/Function | M1 modulation | M2 modulation | Outcomes |
|---|---|---|---|---|
| AMD3100 (Rabinovich-Nikitin et al., 2016) | CXCR4 antagonist | ↓TNF-α, IL-6 | Survival +10%, ↑onset, b.w., motor function | |
| BBG (Apolloni et al., 2014) | P2X7 antagonist | ↓NOX2, IL-1β; n.s.c. TNF-α, IL-6, iNOS | ↑BDNF, IL-10 | Survival n.s.c., ↑motor function |
| Bee venom (Yang et al., 2010) | anti-inflammation | TNF-α↓ | Survival +18%, ↑onset, motor function | |
| Celastrol (Kiaei et al., 2005b) | iNOS↓ | Survival +13%, ↑onset, b.w., motor function | ||
| Celecoxib/Rofecoxib + Creatine (Klivenyi et al., 2004) | COX-2 inhibitor | PGE2↓ | Survival +30%, ↑b.w., motor function | |
| Clemastine (Apolloni et al., 2016b) | Antihistamine | ↓CD68, gp91phox | ↑Arg1, BDNF | Survival n.c.s., ↑onset, |
| DL-NBP (Feng et al., 2012) | Neuroprotection | ↓TNF-α | Survival +42%, ↑b.w., motor function | |
| EGCG (Xu et al., 2006) | Neuroprotection | iNOS↓ | Survival +10%, onset +9%, | |
| hMSC (Zhou et al., 2013) | Stromal cells | ↓TNF-α, iNOS | Survival +10%, onset +6%, ↑motor function | |
| IL-1RA (Meissner et al., 2010) | IL-1R antagonist | Survival +4%, ↑motor function | ||
| Lenalidomide (Kiaei et al., 2006) | ↓ TNF-α | ↓TNF-α, IL-1α, IL-1β | ↑TGF-β1 | Survival +18%, ↑onset, b.w., motor function |
| *M-CSF (Gowing et al., 2009) | Cytokine | ↑TNF-α, IL-1β;↓IL-6, NOX2 | ↓IL-4; ↑TGF-β1 | Survival −3% |
| Minocycline (Kobayashi et al., 2013) | ↓glia activation | ↓TNF-α, IL-1β, INF-γ, CD86, CD68 | n.s.c. CD206, Arg1, IL-4, IL-10, Ym1 | Survival +54%, onset +15% |
| Nimesulide (Pompl et al., 2003) | COX-2 inhibitor | PGE2↓ | Survival n.d., ↑onset, motor function | |
| Pioglitazone (Kiaei et al., 2005a) | PPARγ agonist | ↓iNOS, COX2 | Survival +13%, ↑onset, b.w., motor function | |
| R723 (Tada et al., 2014) | JAK2 inhibitor | ↓CD11b, iNOS; n.s.c. TNF-α, IL6, IL-1β | n.s.c. Arg1, Ym1, IL-4 | n.s.c. |
| scAAV9-VEGF (Wang et al., 2016) | ↑ VEGF | ↓TNF-α, CD68 | ↑Arg1, Ym1 | Survival +10%, ↑b.w., motor function |
| Sulindac (Kiaei et al., 2005c) | COX inhibitor | COX2↓ | Survival +10%, ↑b.w., motor function | |
| Thalidomide (Kiaei et al., 2006) | ↓ TNF-α | ↓TNF-α; n.s.c. IL-1α, IL-1β | ↑TGF-β1 | Survival +12%, ↑onset, b.w., motor function |
| gp91phox− (Wu et al., 2006) | NOX2 inhibition | IL-1β n.s.c. | Survival +11% | |
| IL-1β−/− (Meissner et al., 2010) | IL-1β decrease | ↓IL-1β−/− | Survival +5% | |
| iNOS−/− (Martin et al., 2007) | iNOS inhibition | ↓iNOS | ↑Survival | |
| NOX2−/− (Marden et al., 2007) | NOX2 inhibition | ↓NOX2 | Survival +73%, ↑onset, b.w., motor function | |
| **TNF-α−/− (Gowing et al., 2006) | TNF-α decrease | ↓TNF-α | n.s.c. | |
| *xCT−/− (Mesci et al., 2015) | ↓ Glutamate release | Onset: ↑IL-1β, iNOS E.s.: ↓IL-1β, iNOS |
Onset: ↓Arg1, Ym1 L.s.:↑Arg1, Ym1 |
Survival n.s.c., onset −9%, ↑b.w. (at l.s.), motor function |
All trials were performed in SOD1G93A mice except the cases indicated with asterisks (* performed in SODG37R mice, ** performed both in SODG93A and SODG37R mice). The reported data refer to most effective results obtained in the cited article. Abbreviations: n.d., not described, n.s.c., non significant changes, ↑ increased, ↓ decreased; b.w., body weight, e.s., end stage, l.s., late symptomatic stage.