TLR4 deficiency has a protective effect in the MPTP/probenecid mouse model of Parkinson's disease.

Acta Pharmacologica Sinica
Qian-Hang ShaoNai-Hong Chen

Abstract

Parkinson's disease (PD) is a multifactorial disorder characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the presence of Lewy bodies (LBs) consisting of misfolded α-synuclein protein. The etiology of PD is still not clear but systemic inflammation is proved to trigger and exacerbate DA neurons degeneration. Toll-like receptor 4 (TLR4) is a pattern-recognition receptor (PRR) and plays a major role in promoting the host immune. TLR4-mediated signal pathways induce the release of many inflammatory cytokines. It is reasonable to hypothesize that TLR4 is the mediator in microglia contributing to the damage of DA neurons in the SNpc. In this study, we evaluated the role of TLR4 in the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid mouse model. Both TLR4-deficient and wild-type (WT) mice were injected with probenecid (250 mg/kg, i.p.) followed by injection of MPTP (25 mg/kg, s.c.) every 4 days for 10 times. From D43 to D47, the behavioral performance in pole test and wire hang test was assessed. Then the mice were euthanized, and SN and striatum were dissected out for biochemical tests. We showed that compared with MPTP-treated WT mice, TLR4 deficienc...Continue Reading

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Citations

Jul 9, 2020·Cells·Ádám MészárosIstván A Krizbai
Jul 3, 2021·Frontiers in Cell and Developmental Biology·Sara R OliveiraCecília M P Rodrigues
Jul 3, 2021·Biomolecules·Antía CustodiaAlberto Ouro
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Dec 1, 2021·Essays in Biochemistry·Kishore Aravind Ravichandran, Michael T Heneka

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Methods Mentioned

BETA
electrophoresis

Software Mentioned

GraphPad Prism
Image Pro Plus
Quantity One

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