TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation.

Lorenza Magno, Tom D Bunney, Emma Mead, Fredrik Svensson, Magda N Bictash

Journal: Molecular neurodegeneration 2021;16(1):22

PMID: 33823896

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Abstract

The central role of the resident innate immune cells of the brain (microglia) in neurodegeneration has become clear over the past few years largely through genome-wide association studies (GWAS), and has rapidly become an active area of research. However, a mechanistic understanding (gene to function) has lagged behind. That is now beginning to change, as exemplified by a number of recent exciting and important reports that provide insight into the function of two key gene products - TREM2 (Triggering Receptor Expressed On Myeloid Cells 2) and PLCγ2 (Phospholipase C gamma2) - in microglia, and their role in neurodegenerative disorders. In this review we explore and discuss these recent advances and the opportunities that they may provide for the development of new therapies.

Address: Alzheimer's Research UK UCL Drug Discovery Institute, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK. [email protected].; Institute of Structural and Molecular Biology, Division of Biosciences, University College London, Gower Street, London, WC1E 6BT, UK.; Alzheimer's Research UK Oxford Drug Discovery Institute, Nuffield Department of Medicine Research Building, University of Oxford, Oxford, OX3 7FZ, UK.; Alzheimer's Research UK UCL Drug Discovery Institute, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK.

DOI: 10.1186/s13024-021-00436-5

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https://medlineplus.gov/alzheimersdisease.html

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https://scite.ai/reports/33823896

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https://assays.cancer.gov/CPTAC-68

MeSH Terms: Age of Onset, Alzheimer Disease, Connective Tissue Cells, Humans, Lipid Metabolism, Lymphocytes, Membrane Glycoproteins, Microglia, Models, Molecular, Mutation, Myeloid Cells, Phospholipase C gamma, Protein Conformation, Protein Domains, Protein Interaction Mapping, Receptors, Immunologic, Sequence Homology, Amino Acid, Signal Transduction, Structure-Activity Relationship