By Takaomi Comings Saido
Beta-secretase M. Citron Alpha-secretases S. Ishiura ADAM 10/alpha secretase and presenilins/gamma secretase in APP processing and notch signaling D. Hartmann Gamma-secretase and presenilin M. Wolfe Biochemistry of gamma-secretase (tentative identify) S. Sinha Presenilin and intracellular protein shipping Degradation of Abeta through neprilysin T.C. Saido Degradation of Abeta via endothelin-converting enzyme C. Eckman Degradation of Abeta via insulin-degrading enzyme Lipid raft and Abeta metabolism T. Golde Lipid raft and Abeta accumulation M. Morishima-Kawashima and Y. Ihara Transport-dependent clearance of Abeta B. Zlokovic Abeta vaccination C. Lemere
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Extra resources for A-Beta Metabolism and Alzheimer's Disease (Neuroscience Intelligence Unit 7)
22 Therefore NSAIDs may provide an avenue to prevention of the Alzheimer’s disease. Acknowledgments This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas(C)-Advanced Brain Science Project-from the Ministry of Education, Culture, Sports, Science and Technology, Japan. References 1. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science 2002; 297:353-356. 2. Mills J, Reiner PB. Regulation of amyloid precursor protein cleavage.
The two conserved aspartates required for presenilin endoproteolysis and γ-secretase processing of APP and Notch are predicted to be within TM6 and TM7. The region of the protein encoded by exon 9 is denoted; natural deletion of this exon leads to a noncleavable but functional presenilin. 36,37 Unfortunately, the embryonic lethality resulting from deleting PS1 did not suggest reasons why PS mutations might cause AD relatively late in life. 38 The maturation and distribution of APP was not affected by the deletion of the PS1 gene, nor was the release of α- or β-APPs altered.
Small DH. The role of presenilins in γ-secretase activity: catalyst or cofactor? J Neurochem 2001; 76:1612-1614. 21. Checler F. The multiple paradoxes of presenilins. J Neurochem 2001; 76:1621-1627. 22. Kinouchi T, Ono Y, Sorimachi H et al. Arachidonate metabolites affect the secretion of an N-terminal fragment of Alzheimer’ disease amyloid precursor protein. Biochem Biophys Res Commun 1995; 209:841-849. CHAPTER 4 γ-Secretase and Presenilin Michael S. Wolfe Abstract B ecause production and deposition of the amyloid-β peptide (Aβ) is intimately linked to the pathogenesis of Alzheimer’s disease (AD), the proteases responsible for excising Aβ from the amyloid-β precursor protein (APP), β- and γ-secretases, are considered important therapeutic targets.
A-Beta Metabolism and Alzheimer's Disease (Neuroscience Intelligence Unit 7) by Takaomi Comings Saido