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P4‐304: STAT3 Signaling Referees Microglial Amyloid Clearance in Alzheimer’S Disease
Author(s) -
Doty Kevin R.,
Guillot-Sestier Marie-Victoire,
Town Terrence
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.07.047
Subject(s) - microglia , phagocytosis , neuroinflammation , biology , microbiology and biotechnology , amyloid (mycology) , alzheimer's disease , immunology , senile plaques , stat3 , neuroscience , signal transduction , medicine , inflammation , pathology , disease
tion in the Golgi and also shows greatly impaired cell surface expression. Surprisingly, we find that these mutants appear to be exported from the endoplasmic reticulum (ER) without defect. The results suggest the existence of an efficient protein recycling pathway that returns mutant TREM2 to the ER after export. Intriguingly, we find that all mutants that fail to undergo maturation also display a propensity to form a stable homodimer that is not dissociated by SDS, urea, reducing agents or heating. Because all mutations producing this effect localize to the extracellular, Ig-like domain, the results suggest an important role for this domain in regulating the biochemical characteristics of TREM2. Conclusions: Our findings suggest that disease-causing TREM2 mutations may result in early-onset neurodegeneration via loss of cell surface expression, and imply that a common biochemical abnormality is induced by pathogenic mutations within the Ig-like domain.