Receptor –ligand interaction controls microglial chemotaxis and amelioration of Alzheimer's disease pathology

In this review, we highlight the importance of microglial chemotaxis in promoting the clearance of danger-associated molecular patterns in Alzheimer's disease (AD). We further discuss how microglial receptor –ligand signalings, including TREM2, CD33, IL-3/IL-3R, IL-33/ST2, and CCL2/CCR2 pathways, and the dysregulation of decoy receptor milieus impair microglial chemotaxis along AD progression. Further detailed investigations are essential to identify the molecular machinery that controls microglial ch emotaxis in AD, which facilitates the development of microglia-targeting AD therapies. AbstractMicroglia maintain brain homeostasis through their ability to survey and phagocytose danger-associated molecular patterns (DAMPs). In Alzheimer's disease (AD), microglial phagocytic clearance regulates the turnover of neurotoxic DAMPs including amyloid beta (A β) and hyperphosphorylated tau. To mediate DAMP clearance, microglia express a repertoire of surface receptors to sense DAMPs; the activation of these receptors subsequently triggers a chemotaxis-to-phagocytosis functional transition in microglia. Therefore, the interaction between microglial recep tors and DAMPs plays a critical role in controlling microglial DAMP clearance and AD pathogenesis. However, there is no comprehensive overview on how microglial sensome receptors interact with DAMPs and regulate various microglial functions, including chemotaxis and phagocytosis. In this review, we discuss the important axes of rece...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: REVIEW Source Type: research