Emerging roles for ITAM and ITIM receptor signaling in microglial biology and Alzheimer's disease‐related amyloidosis
Year: 2023
Type: article
Abstract: Microglia are critical responders to amyloid beta (Aβ) 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 periphery. In this review, we summarize the diverse functions employed by microglia in response to Aβ plaques and also discuss the innate immune receptors and intracellular signaling players that guide these functions. Specifically, we focus on the role of ITAM and ITIM signaling cascades in regulating microglia innate immune responses. A better understanding of how microglial innate immune responses are regulated in AD may provide novel therapeutic avenues to tune the microglial innate immune response in AD pathology.
Source: Journal of Neurochemistry
DOI: 10.1111/jnc.15981
Institution: University of Virginia
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,840
Funders: Alzheimer's Association, Cure Alzheimer's Fund, Owens Family Foundation, National Institutes of Health, Brain Institute, University of Virginia, National Institute on Aging, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering
Awards: G1016190154, G1165452551, G1185801986, AIMing at DNA damage sensors to take the STING out of Alzheimer’s disease, Inflammasome activation and lymphatic dysfunction in traumatic brain injury, CLEC7A in microglia biology and Alzheimer's disease, G499753431, G6447527400, G8034097905, G9000210780, G9000224343
OpenAlex ID: W4387564138
