Emerging roles for ITAM and ITIM receptor signaling in microglial biology and Alzheimer's disease ‐related amyloidosis

Microglia are increasingly implicated in Alzheimer's disease (AD) where they are key responders to amyloid beta plaques. While previous studies have focused on the innate immune receptors driving microglia immune responses, how microglial innate immune responses are regulated is less understood. Immunoreceptor tyrosine-based activating and inhibitory motifs (ITAM/ITIM) are commonly known to regulate innate immune responses in the periphery. Here, we review how microglia utilize ITAM- and ITIM-mediated signaling to regulate immune responses in AD amyloidosis. A better understanding of how microglial immune responses are regulated may provide novel therapeutic avenues to tune the microglial innate immune response in AD pathology. AbstractMicroglia are critical responders to amyloid beta (A β) plaques in Alzheimer's disease (AD). Therefore, the therapeutic targeting of microglia in AD is of high clinical interest. While previous investigation has focused on the innate immune receptors governing microglial functions in response to Aβ plaques, how microglial innate immune responses are regulated is not well understood. Interestingly, many of these microglial innate immune receptors contain unique cytoplasmic motifs, termed immunoreceptor tyrosine-based activating and inhibitory motifs (ITAM/ITIM), that are commonly known to regulate immune activation and inhibition in the periphe ry. In this review, we summarize the diverse functions employed by microglia in response to Aβ plaq...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: REVIEW Source Type: research