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Deletion of tumor necrosis factor death receptor inhibits amyloid beta generation and prevents learning and memory deficits in Alzheimer's mice.

Authors: He, Ping  Zhong, Zhenyu  Lindholm, Kristina  Berning, Lilian  Lee, Wendy  Lemere, Cynthia  Staufenbiel, Matthias  Li, Rena  Shen, Yong 
Citation: He P, etal., J Cell Biol. 2007 Aug 27;178(5):829-41. doi: 10.1083/jcb.200705042.
Pubmed: (View Article at PubMed) PMID:17724122
DOI: Full-text: DOI:10.1083/jcb.200705042

The tumor necrosis factor type 1 death receptor (TNFR1) contributes to apoptosis. TNFR1, a subgroup of the TNFR superfamily, contains a cytoplasmic death domain. We recently demonstrated that the TNFR1 cascade is required for amyloid beta protein (Abeta)-induced neuronal death. However, the function of TNFR1 in Abeta plaque pathology and amyloid precursor protein (APP) processing in Alzheimer's disease (AD) remains unclear. We report that the deletion of the TNFR1 gene in APP23 transgenic mice (APP23/TNFR1(-/-)) inhibits Abeta generation and diminishes Abeta plaque formation in the brain. Genetic deletion of TNFR1 leads to reduced beta-secretase 1 (BACE1) levels and activity. TNFR1 regulates BACE1 promoter activity via the nuclear factor-kappaB pathway, and the deletion of TNFR1 in APP23 transgenic mice prevents learning and memory deficits. These findings suggest that TNFR1 not only contributes to neurodegeneration but also that it is involved in APP processing and Abeta plaque formation. Thus, TNFR1 is a novel therapeutic target for AD.


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CRRD Object Information
CRRD ID: 13825267
Created: 2018-12-05
Species: All species
Last Modified: 2018-12-05
Status: ACTIVE


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