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F2‐01‐06: The Retromer Pathway Links Obesity and Diabetes to Alzheimer's Disease
Author(s) -
Small Scott
Publication year - 2011
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.2011.05.820
Subject(s) - retromer , biology , vacuolar protein sorting , neuroscience , genetics , endosome , receptor
hances APP retrieval via a retromer-mediated process. This APP S655E phosphomimetic mutant also displayed decreased APP lysosomal targeting, enhanced mature half-life, and decreased tendency towards Abeta production. It follows that VPS35 downregulation impairs the phosphorylation dependent APP retrieval to the TGN, and decreases APP half-life. Conclusions: These results permit concluding that APP phosphorylation on S655 regulates its fate in terms of retromer-mediated sorting to the TGN or lysosomal targeting. Furthermore, the data are consistent with known interactions involving the retromer, SorLA and APP. These findings add to our understanding of APP targeting and the molecular basis of sporadic AD pathogenesis; representing putative new targets for AD diagnostic and therapeutic approaches.