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.
Keywords:
Alzheimer’s disease; Immune system; Microglia; Protein networks; Signalling; Therapeutic intervention.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Age of Onset
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Alzheimer Disease / drug therapy
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Alzheimer Disease / genetics
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Alzheimer Disease / immunology*
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Alzheimer Disease / prevention & control
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Connective Tissue Cells / metabolism*
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Humans
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Lipid Metabolism
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Lymphocytes / metabolism*
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / physiology*
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Microglia / metabolism*
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Microglia / physiology
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Models, Molecular
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Mutation
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Myeloid Cells / metabolism*
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Phospholipase C gamma / chemistry
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Phospholipase C gamma / genetics
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Phospholipase C gamma / physiology*
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Protein Conformation
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Protein Domains
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Protein Interaction Mapping
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Receptors, Immunologic / chemistry
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Receptors, Immunologic / physiology*
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Sequence Homology, Amino Acid
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Signal Transduction / physiology*
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Structure-Activity Relationship
Substances
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Membrane Glycoproteins
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Receptors, Immunologic
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TREM2 protein, human
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Phospholipase C gamma