Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7302944 | Neuroscience & Biobehavioral Reviews | 2016 | 50 Pages |
Abstract
The innate immunity is a stereotyped first line of defense against pathogens and unspecified damage signals. One of main actors of innate immunity are the Toll-like receptors (TLRs), and one of the better characterized members of this family is TLR-4, that it is mainly activated by Gram-negative bacteria lipopolysaccharide. In brain, TLR-4 organizes innate immune responses against infections or cellular damage, but also possesses other physiological functions. In the last years, some evidences suggest a role of TLR-4 in stress and stress-related neuropsychiatric diseases. Peripheral and brain TLR-4 activation triggers sickness behavior, and its expression is a risk factor of depression. Some elements of the TLR-4 signaling pathway are up-regulated in peripheral samples and brain post-mortem tissue from depressed and suicidal patients. The “leaky gut” hypothesis of neuropsychiatric diseases is based on the existence of an increase of the intestinal permeability which results in bacterial translocation able to activate TLR-4. Enhanced peripheral TLR-4 expression/activity has been described in subjects diagnosed with schizophrenia, bipolar disorder and in autistic children. A role for TLR-4 in drugs abuse has been also proposed. The therapeutic potential of pharmacological/genetic modulation of TLRs signaling pathways in neuropsychiatry is promising, but a great preclinical/clinical scientific effort is still needed.
Keywords
TIRAPCD14IKKIκBαTABIRFAP-1p38TRAFMD2ERKToll-interleukin 1 receptor (TIR) domain containing adaptor proteininhibitor of NFκBMYD88TAK1-binding proteinJnkTAKc-Jun N-terminal kinaseMAPKsNFκBTRIFSTATStressSchizophreniaDepressioninflammationmyeloid differentiation primary response 88Innate immunityTIR-domain-containing adapter-inducing interferon-βTRAMcluster of differentiation 14interferon regulatory factorTNF receptor associated factorIRAKnuclear factor kappa BSignal transducer and activator of transcriptionMEKTRIF-related adaptor moleculeactivator proteinmitogen-activated protein kinasep38 mitogen-activated protein kinaseMAP kinasesextracellular signal-regulated kinaseIL-1 receptor-associated kinaseToll-like receptors
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Authors
B. GarcÃa Bueno, J.R. Caso, J.L.M. Madrigal, J.C. Leza,