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Biotech / Medical : momo-T/FIF -- Ignore unavailable to you. Want to Upgrade?

To: keokalani'nui who wrote (430)	5/30/2004 9:04:19 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 12215

embargo........ abstractsonline.com type "flurbiprofen" into the search field.

To: keokalani'nui who wrote (430)	5/30/2004 9:25:02 PM
From: scaram(o)uche	Respond to of 12215

sounds like a major, biggie prospective study, Zandi et al. plus the Golde et al. work, and Imbimbo et al. sounds like major validation. when you're done with that, look at the abstract by Jeffrey S. Nye. JNJ Phramaceutical R&D. the presentation by Thomas Kukar will be interesting, although it's not clear to me what the final version may be. but, clearly, Zandi et al. is what I've been looking for...... something that can or flat out won't validate, prior to 1Q04.

To: keokalani'nui who wrote (430)	5/30/2004 10:52:08 PM
From: scaram(o)uche	Respond to of 12215

Selkoe et al....... Presenilin as the Active Site of Gamma-Secretase, a Novel Intramembranous Aspartyl Protease

To: keokalani'nui who wrote (430)	5/30/2004 10:59:56 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 12215

you, of course, know this....... pubmedcentral.nih.gov pubmedcentral.nih.gov Flurbiprofen and its enantiomers directly target ã-secretase. ã-Secretase refers to the enzymatic activity that carries out the final cleavage to release Aâ from APP carboxy-terminal fragments (CTFs) (1). ã-Secretase activity resides in a high-molecular-weight complex that consists of four proteins, either PS1 or PS2 coupled with nicastrin, APH-1, and PEN-2 (26, 27). Although the precise role of each member of the complex is not definitively proven, it appears that the PSs are the catalytic subunits (28). Because NSAIDs appear to shift ã-secretase cleavage independently of known cellular targets, we used a well-characterized broken cell ã-secretase assay to determine whether flurbiprofen and its enantiomers directly target ã-secretase (21, 22). This assay uses partially purified carbonate-stripped membranes that are enriched for ã-secretase activity and contain endogenous APP CTFs as substrate. Importantly, no detergents are used in this assay, since we find that solublization of ã-secretase with detergents can alter the response to various inhibitors and Aâ42 lowering NSAIDs (data not shown). Flurbiprofen and its enantiomers lower Aâ42 levels in the broken cell ã-secretase assay with a dose response similar to what was observed for cell culture without significantly affecting either Aâ40 production (Figure 3) or CTFã production (data not shown).