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http://purl.uniprot.org/citations/24052255http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24052255http://www.w3.org/2000/01/rdf-schema#comment"Recent studies link synaptojanin 1 (synj1), the main phosphoinositol (4,5)-biphosphate phosphatase (PI(4,5)P2-degrading enzyme) in the brain and synapses, to Alzheimer disease. Here we report a novel mechanism by which synj1 reversely regulates cellular clearance of amyloid-β (Aβ). Genetic down-regulation of synj1 reduces both extracellular and intracellular Aβ levels in N2a cells stably expressing the Swedish mutant of amyloid precursor protein (APP). Moreover, synj1 haploinsufficiency in an Alzheimer disease transgenic mouse model expressing the Swedish mutant APP and the presenilin-1 mutant ΔE9 reduces amyloid plaque load, as well as Aβ40 and Aβ42 levels in hippocampus of 9-month-old animals. Reduced expression of synj1 attenuates cognitive deficits in these transgenic mice. However, reduction of synj1 does not affect levels of full-length APP and the C-terminal fragment, suggesting that Aβ generation by β- and γ-secretase cleavage is not affected. Instead, synj1 knockdown increases Aβ uptake and cellular degradation through accelerated delivery to lysosomes. These effects are partially dependent upon elevated PI(4,5)P2 with synj1 down-regulation. In summary, our data suggest a novel mechanism by which reduction of a PI(4,5)P2-degrading enzyme, synj1, improves amyloid-induced neuropathology and behavior deficits through accelerating cellular Aβ clearance."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m113.504365"xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Liu L."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Zhu L."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Zhao J."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Zhong M."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Gandy S.E."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Robakis N.K."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Volpicelli-Daley L."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Cai D."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Ehrlich M.E."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Lucast L."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Knight E.M."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Rhee H."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Bustos V."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Caesar I."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/author"Netzer W."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/pages"32050-32063"xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/title"Reduction of synaptojanin 1 accelerates Abeta clearance and attenuates cognitive deterioration in an Alzheimer mouse model."xsd:string
http://purl.uniprot.org/citations/24052255http://purl.uniprot.org/core/volume"288"xsd:string
http://purl.uniprot.org/citations/24052255http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24052255
http://purl.uniprot.org/citations/24052255http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24052255