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S3–02–03: Disease modification: From etiological hypothesis to clinical testing
Author(s) -
Poirier Judes
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.169
Subject(s) - apolipoprotein e , probucol , medicine , endocrinology , cholesterol , tacrine , pharmacology , biology , disease , biochemistry , enzyme , acetylcholinesterase
These regulatory cycles are equally effective in primary neurons, human neuroblastoma cell culture lines as well as a variety of APP expressing peripheral cells and cells of rodent, primate and human origin. Two metabolic enzymes were identified to be regulated by A . Remarkably, both enzymes (HMG-Co A reductase for A 40 and SMase for A 42) were previously shown to represent the main regulatory enzymes in their respective homeostatic pathways, already indicating that A function for lipid homeostasis is essential and of critical relevance. Indeed, knock-out of presenilin or APP in mice abolishes cholesterol and sphingomyelin down-regulation. Whereas A -feeding of APP or PS I/II knock-out cells recovers cholesterol and sphingomyelin regulation. The strict necessity of PS I and PS II for APP cleavage in A mediated lipid homeostasis shows close relation to cholesterol and sphingomyelin regulation by SREBP cleavage and signaling, indicating the additional involvement of higher level regulatory cycles.