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Toll‐like receptors in neuroinflammation, neurodegeneration, and alcohol‐induced brain damage
Author(s) -
Pascual María,
CalvoRodriguez Maria,
Núñez Lucía,
Villalobos Carlos,
Ureña Juan,
Guerri Consuelo
Publication year - 2021
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.2510
Subject(s) - neuroinflammation , neurodegeneration , microbiology and biotechnology , innate immune system , biology , microglia , proinflammatory cytokine , pattern recognition receptor , receptor , trif , signal transduction , immune system , neuroscience , inflammation , toll like receptor , immunology , medicine , disease , pathology , biochemistry
Toll‐like receptors (TLRs) or pattern recognition receptors respond to pathogen‐associated molecular patterns (PAMPs) or internal damage‐associated molecular patterns (DAMPs). TLRs are integral membrane proteins with both extracellular leucine‐rich and cytoplasmic domains that initiate downstream signaling through kinases by activating transcription factors like AP‐1 and NF‐κB, which lead to the release of various inflammatory cytokines and immune modulators. In the central nervous system, different TLRs are expressed mainly in microglia and astroglial cells, although some TLRs are also expressed in oligodendroglia and neurons. Activation of TLRs triggers signaling cascades by the host as a defense mechanism against invaders to repair damaged tissue. However, overactivation of TLRs disrupts the sustained immune homeostasis‐induced production of pro‐inflammatory molecules, such as cytokines, miRNAs, and inflammatory components of extracellular vesicles. These inflammatory mediators can, in turn, induce neuroinflammation, and neural tissue damage associated with many neurodegenerative diseases. This review discusses the critical role of TLRs response in Alzheimer's disease, Parkinson's disease, ischemic stroke, amyotrophic lateral sclerosis, and alcohol‐induced brain damage and neurodegeneration.