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Table 2 Substance affecting TLRs and neuroinflammation in PD

From: The role of Toll-like receptors and neuroinflammation in Parkinson’s disease

Name of substance Type of evidence Sample Effect of therapy Year References
Vinpocetine Clinical A cohort of 89 Parkinson’s disease patients and 42 healthy controls Administration of vinpocetine reduced mRNA levels of TLR2/4 and protein levels of MyD88 and NF-kB; and it reduced the levels of serum inflammatory cytokines 2019 [140]
Cordycepin Animal/in vitro MPTP-induced murine model and LPS-induced cell model of PD Cordycepin improved PD symptoms by inhibiting TLR/NF-kB signaling pathway in vivo and in vitro 2019 [113]
SA00025 (a nuclear receptor-related 1 agonist) Animal/in vitro Rats administered by a TLR3 agonist (poly I:C) and 6-OHDA It caused neuroprotective and anti-inflammatory effects in animal model of PD 2015 [159]
Peroxiredoxin 6 Animal/in vitro PRDX6-overexpressing transgenic (Tg) mice and wild-type mice PRDX6 inhibited the neurogenesis by TLR4-dependent pathway contributing to symptoms in this genetic model of PD 2019 [126]
Fecal microbial transplantation (FMT) Animal/in vitro PD mice FMT reduced expression of TLR4/TNF-α signaling pathway components in gut and brain and suppressed neuroinflammation 2018 [160]
Dihydrotestosterone (DHT) Animal/in vitro LPS-induced mice model DHT induced anti-neuroinflammatory and neuroprotective effects, inhibiting inflammatory cytokine production through TLR4 2020 [129]
Hesperetin Animal/in vitro LPS-induced BV2 cells of mice Hesperetin treatment alleviated proinflammatory cytokine production by ameliorating TLR4-mediated ionized calcium-binding adapter molecule 1/glial fibrillary acidic protein (Iba-1/GFAP) expression 2019 [132]
Icariside II (ICS II) Animal/in vitro LPS-infused rats ICS could attenuate LPS-induced neuroinflammation by inhibiting TLR4/MyD88/NF-kB pathway in rats 2019 [134]
Monophosphoryl lipid A (a TLR4 agonist) Animal/in vitro Transgenic mice overexpressing α-synuclein (proteolipid protein promoter-α-syn mouse model) Chronic systemic MPLA treatment led to increased uptake of α-synuclein by microglial cells, pronounced motor improvement, and rescue of DA neurons 2017 [161]
CU-CPT22 (candesartan cilexetil) Animal/in vitro BV2 mice microglial cells CU-CPT22 reduced the nuclear translocation of NF-κB and secretion of TNF-α from cultured primary mouse microglia
Candesartan cilexetil reversed the proinflammatory phenotype of primary mice microglia induced by α-synuclein
2015 [88]
Prothrombin kringle-2 (pKr-2) Animal/in vitro Rat and mouse brain injected with pKr-2 Microglial TLR4 was upregulated in the rat SN and in cultures of the BV2 microglial cell line after PKr-2 treatment 2015 [162]
Asiatic acid (AA) Animal/in vitro MPTP mouse model of PD AA treatments reduced striatal expression of α-synuclein and TLR4, increased striatal levels of dopamine, brain-derived nerve growth factor, and glial cell line-derived neurotrophic factor 2016 [92]
  1. TLR toll-like receptor, MPTP 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, PD Parkinson’s disease, pKr-2 prothrombin kringle-2, NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells, mRNA messenger RNA, MPLA: monophosphoryl lipid A, DA: dopaminergic, TNF-α: tumor necrosis factor-α, 6-OHDA: 6-hydroxydopamine, poly I:C: polyinosinic:polycytidylic acid.