Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain.

  title={Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain.},
  author={Harry F. Dovey and Varghese John and John P. Anderson and Lucy Zhuo Chen and P de Saint Andrieu and Larry Y Fang and Stephen B. Freedman and Britta M Folmer and Erich G Goldbach and Elzbieta J Holsztynska and Kopecko Lan Hu and Kelly Johnson-wood and Sarah L Kennedy and Dora Kholodenko and Jeroen E Knops and Lee H Latimer and Mike X Lee and Zhongji Liao and Ivan M. Lieberburg and Ruth N Motter and Linda Mutter and J Nietz and Kevin P. Quinn and Karna L. Sacchi and Peter Seubert and Geogre M. Shopp and Eugene D Thorsett and Jay S Tung and Jing Wu and Sufang Yang and Chunhua Yin and Dale B. Schenk and Patrick C. May and L D Altstiel and Matthew H Bender and Leonard N Boggs and Thomas C. Britton and James C. Clemens and Dan L Czilli and D K Dieckman-McGinty and James J. Droste and K. S. Fuson and Bruce D Gitter and Paul A Hyslop and Edward M. Johnstone and Wanda Y. Li and Sheila P. Little and Thomas E Mabry and F. D. Miller and James E Audia},
  journal={Journal of neurochemistry},
  volume={76 1},
Converging lines of evidence implicate the beta-amyloid peptide (Ass) as causative in Alzheimer's disease. We describe a novel class of compounds that reduce A beta production by functionally inhibiting gamma-secretase, the activity responsible for the carboxy-terminal cleavage required for A beta production. These molecules are active in both 293 HEK cells and neuronal cultures, and exert their effect upon A beta production without affecting protein secretion, most notably in the secreted… CONTINUE READING
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