Toll-like receptors in neurodegeneration
Journal
Brain Research Reviews
Journal Volume
59
Journal Issue
2
Pages
278-292
Date Issued
2009
Author(s)
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.
SDGs
Other Subjects
cell adhesion molecule; cytokine; phosphotransferase; toll like receptor; Alzheimer disease; astrocyte; cerebrovascular accident; cytokine production; human; inflammation; microglia; multiple sclerosis; nerve cell lesion; nerve cell plasticity; nerve degeneration; nerve fiber growth; nervous system development; nonhuman; oligodendroglia; priority journal; protein domain; protein expression; protein function; review; signal transduction; stroke; Animals; Central Nervous System; Encephalitis; Humans; Immune System; Inflammation Mediators; Lymphocytes; Neurodegenerative Diseases; Neuroglia; Signal Transduction; Toll-Like Receptors
Type
review