Table 1.
The main TLR-modulatory compounds carrying in vitro and/or in vivo activity to counteract inflammation in PD models
| Name | Activity | Model/Study | Effects |
|---|---|---|---|
| Vinpocetine | Decreases mRNA levels of TLR2, TLR4, MyD88, and NF-κB | Patients with PD, double-blind placebo control study [81] | Decreased serum levels of pro-inflammatory cytokines, induced TLR3 and serum anti-inflammatory substances. Not clear the effects on cognitive function |
| Functional antibody | TLR2 antagonist | Murine PD model [82] | Decreased α-syn aggregation and deposition, lowered neuroinflammation, neurodegeneration and behavioral symptoms |
| Farrerol | TLR4 inhibitor | Murine PD model [83] | Decreased production of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β; increased inhibition of NF-κB |
| Kaempferol | Down-regulation of TLR4-mediated pathway | Murine PD model [84] | Decreased production of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β; decreased neuronal injury |
| Hesperetin | Down-regulation of TLR4-mediated pathway | Murine PD model [85] | Improved cognition, memory and synaptic plasticity |
| Candesartan | Antihypertensive medication decreasing TLR2 expression | Cultured primary microglia [86] | Shifted primary microglia status from pro-inflammatory to anti-inflammatory |
| CU-CPT22 | TLR1/2 heterodimer inhibitor | Cultured primary microglia [86] | Decreased production of pro-inflammatory cytokines, including TNF-α and IL-1β; decreased translocation of NF-κB |
| Schisandrin B | Inhibitor of interaction between TLR4 and regulatory proteins (MyD88, TRAF-6) | Cultured microglia; murine PD model [87] | Decreased production of pro-inflammatory cytokines, including TNF-α, IL-6, PGE2, and IL-1β, and ROS; inhibition of NADPH oxidase |
| Dihydrotestosterone (DHT) | Inhibitor of TLR4-dependent NF-kB and MAPK p38 pathways | Cultured microglia; murine PD model [88] | Decreased production of pro-inflammatory cytokines, improvement of neurocognitive tests |
| Silymarin | Suppresses TLR4-dependent pathway | Murine PD model [89] | Neuroprotective effects on dopaminergic neurons, by reducing neuronal apoptosis |
| Icariside II | Inhibitor of TLR4/MyD88/NF-kB pathway | Murine PD model [90] | Decreases pro-inflammatory cytokines production, and astrocyte activation [85–87] |
| Fecal microbiota transplantation (FMT) | Among others, decreases TLR4 gut and brain expression | Murine PD model [91] | Increase in striatal dopamine, reversal of microglial and astrocyte activation, decreased TLR4 gut and brain expression |