Microglial ITAM & ITIM signaling in neurodegenerative disease and brain aging.

Aman Mangalmurti, Amelia Bonheur, John R Lukens

Center for Brain Immunology and Glia (BIG), Harrison Family Translational Research Center in Alzheimer's and Neurodegenerative Diseases, Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA; Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.Center for Brain Immunology and Glia (BIG), Harrison Family Translational Research Center in Alzheimer's and Neurodegenerative Diseases, Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA; Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA. · pubmed

Paper

Abstract

Innate immunity within the central nervous system (CNS) plays key roles in shaping both healthy brain aging and vulnerability to neurodegenerative disease. Microglia, the tissue-resident macrophages of the CNS, play a key role in mediating the innate immune responses to age-associated pathologies. A growing body of literature details the roles of microglia in responding to white matter degeneration, misfolded proteins, and cell death. These functions depend on cell-surface receptors that enable microglia to sample and react to changes in their environment. Recent studies highlight the importance of receptors associated with immunoreceptor tyrosine-based activation and inhibitory motifs (ITAMs/ITIMs) in pathological brain aging. In this review, we describe how ITAM/ITIM-associated receptors and their downstream signaling pathways shape microglial responses to neurodegenerative disease and aging. A deeper understanding of microglial activation and resolution may provide tools to harness these cells' capacity to maintain and extend neurological healthspan.

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Research summary

The paper discusses the role of microglial ITAM/ITIM signaling in neurodegenerative diseases and brain aging. This research is relevant as it explores mechanisms that could potentially address the underlying processes of aging and neurodegeneration, rather than merely treating symptoms.

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