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Role of RanBP9 on amyloidogenic processing of APP and synaptic protein levels in the mouse brain.

FASEB J.. 2012-05;  26(5):2072-83
Lakshmana MK, Hayes CD, Bennett SP, Bianchi E, Reddy KM, Koo EH, Kang DE. Section of Neurobiology, Torrey Pines Institute for Molecular Studies, Port Saint Lucie, Florida, USA
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摘要

We previously reported that RanBP9 binds low-density lipoprotein receptor-related protein (LRP), amyloid precursor protein (APP), and BACE1 and robustly increased Aβ generation in a variety of cell lines and primary neuronal cultures. To confirm the physiological/ pathological significance of this phenotype in vivo, we successfully generated transgenic mice overexpressing RanBP9 as well as RanBP9-null mice. Here we show that RanBP9 overexpression resulted in >2-fold increase in Aβ40 levels as early as 4 mo of age. A sustained increase in Aβ40 levels was seen at 12 mo of age in both CHAPS-soluble and formic acid (FA)-soluble brain fractions. In addition, Aβ42 levels were also significantly... More

关键词

Alzheimer's disease; transgenic mice; null mices; ynapses