Toll-like receptors in neurodegeneration

Eitan Okun, Kathleen J. Griffioen, Justin D. Lathia, Sung Chun Tang, Mark P. Mattson, Thiruma V. Arumugam

Research output: Contribution to journalArticle

Abstract

The key roles of toll-like receptors (TLRs) as mediators of the detection and responses of immune cells to invading pathogens are well known. There are at least 13 mammalian TLRs which are integral membrane proteins with a leucine-rich extracellular domain and a cytoplasmic domain similar to that of the interleukin-1 receptor which initiates downstream signaling through kinases to activate transcription factors such as AP-1 and NFκB. TLRs are activated in glial cells (microglia, astrocytes and oligodendrocytes) and lymphocytes that infiltrate the nervous system in response to inflammation caused by infectious agents, tissue injury or autoimmune conditions. By inducing the production of pro-inflammatory cytokines and cell adhesion molecules in immune cells, TLRs may indirectly damage neurons in conditions such as ischemic stroke and multiple sclerosis. Recent findings suggest that neurons also express a subset of TLRs and that their activation promotes neuronal degeneration in experimental models of stroke and Alzheimer's disease. TLRs may also play roles in regulating the processes of neurogenesis and neurite outgrowth, suggesting roles in neuronal plasticity. A better understanding of the molecular and cellular biology of TLRs in the normal and diseased nervous system, may lead to novel approaches for preventing neuronal degeneration and promoting recovery of function in an array of neurodegenerative conditions.

Original languageEnglish (US)
Pages (from-to)278-292
Number of pages15
JournalBrain Research Reviews
Volume59
Issue number2
DOIs
Publication statusPublished - Mar 2009
Externally publishedYes

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Keywords

  • Alzheimer's disease
  • Multiple sclerosis
  • Neurodegeneration
  • Stroke
  • Toll-like receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Okun, E., Griffioen, K. J., Lathia, J. D., Tang, S. C., Mattson, M. P., & Arumugam, T. V. (2009). Toll-like receptors in neurodegeneration. Brain Research Reviews, 59(2), 278-292. https://doi.org/10.1016/j.brainresrev.2008.09.001