Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 311, Issue -, Pages 1-9Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2017.07.009
Keywords
DDRs; Parkinson; Alzheimer; TREM2; Microglia
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The role of cell surface tyrosine kinase collagen-activated receptors known as discoidin domain receptors (DDRs) is unknown in neurodegenerative diseases. We detect up-regulation in DDRs level in post-mortem Alzheimer and Parkinson brains. Lentiviral shRNA knockdown of DDR1 and DDR2 reduces the levels of a-synuclein, tau, and beta-amyloid and prevents cell loss in vivo and in vitro. DDR1 and DDR2 knockdown alters brain immunity and significantly reduces the level of triggering receptor expressed on myeloid cells (TREM)-2 and microglia. These studies suggest that DDR1 and DDR2 inhibition is a potential target to clear neurotoxic proteins and reduce inflammation in neurodegeneration.
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