TLR-Mediated Signal Transduction and Neurodegenerative Disorders

Abstract

A special class of proteins called Toll-like receptors (TLRs) are an essential part of the innate immune system, connecting it to the adaptive immune system. There are 10 different Toll-Like Receptors that have been identified in human beings. TLRs are part of the central nervous system (CNS), showing that the CNS is capable of the immune response, breaking the long-held belief of the brain's "immune privilege" owing to the blood-brain barrier (BBB). These Toll-Like Receptors are present not just on the resident macrophages of the central nervous system but are also expressed by the neurons to allow them for the production of proinflammatory agents such as interferons, cytokines, and chemokines; the activation and recruitment of glial cells; and their participation in neuronal cell death by apoptosis. This study is focused on the potential roles of various TLRs in various neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD), namely TLR2, TLR3, TLR4, TLR7, and TLR9 in AD and PD in human beings and a mouse model.

Keywords: Alzheimer’s disease; TLRs; neurodegeneration Parkinson’s disease; neuroinflammation; neuroprotection.

Figure 1

TLRs and their different adaptors in signal transduction pathways.

Figure 2

Schematic representation of the various elements involved in MyD88-dependent and MyD88-independent signal transduction, using TLR4 as a model molecule.