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Review
. 2022 Mar;395(3):285-294.
doi: 10.1007/s00210-021-02198-9. Epub 2022 Jan 6.

Lipopolysaccharide induced altered signaling pathways in various neurological disorders

Sukhdev Singh  1   2 , Kuleshwar Sahu  1   2 , Charan Singh  3   2 , Arti Singh  4   5
Affiliations
Review

Lipopolysaccharide induced altered signaling pathways in various neurological disorders

Sukhdev Singh et al. Naunyn Schmiedebergs Arch Pharmacol. 2022 Mar.

Abstract

Neuroinflammation is defined as an inflammatory response within the brain or spinal cord, whereas the brain's innate immune system is triggered by various inflammatory challenges such as injury, infection, exposure to toxin (LPS) and ageing, which result in cognitive impairment and neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Lipopolysaccharide (LPS) is a main structural component of the outer membrane of gram-negative bacteria, widely used systematically to stimulate the immune system and to generate profound physiological and behavioural changes. It consists of three parts: lipid A, a core oligosaccharide and an O side chain. It is reported by several scientists that, besides the systemic alteration, LPS also induces neurodegeneration by promoting neuroinflammation upon binding with the stimulation of Toll-like receptor-4 (TLR4) receptors present on glial cells. The mammalian Toll-like receptor (TLR) family consists of 13 membranes and TLR was discovered as a crucial pattern recognition receptor (PPR) involved in the recognition of pathogen-associated molecular patterns (PAMPs). Future studies will show that damage/danger-associated molecular patterns (DAMPs) are recognised by the involvement of PPRs, generated by the host itself. The stimulation of TLR4 by lipopolysaccharide phosphorylates two signalling pathways, namely the MyD88-dependent pathway and the MyD88-independent pathway. This activation subsequently triggers the release of various pro-inflammatory cytokines that are necessary to activate innate immune responses, and then promotes neuroinflammation. In this review, we critically demonstrated the epidemiology of neuroinflammation, types of TLRs, the molecular mechanism of TLR4 and management of neuroinflammation.

Keywords: Lipopolysaccharide; MyD88-dependent; MyD88-independent; Neuroinflammation; Toll-like receptor.

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References

    1. Abg Abd Wahab DY, Gau CH, Zakaria R, Muthu Karuppan MK, Abdullah Z, Alrafiah A, Abdullah JM, Muthuraju S (2019) Review on cross talk between neurotransmitters and neuroinflammation in striatum and cerebellum in the mediation of motor behaviour. BioMed Res Int 2020:1–11 - DOI
    1. Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124(4):783–801 - PubMed - DOI
    1. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413(6857):732–738 - PubMed - DOI
    1. Bao LH, Zhang YN, Zhang JN, Gu L, Yang HM, Huang YY, Xia N, Zhang H (2018) Urate inhibits microglia activation to protect neurons in an LPS-induced model of Parkinson’s disease. J Neuroinflammation 15(1):1–4 - DOI
    1. Bauer S, Kirschning CJ, Häcker H, Redecke V, Hausmann S, Akira S, Wagner H, Lipford GB (2001) Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci 98(16):9237–9242 - PubMed - PMC - DOI

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