The presenilin-1 and -2 (PS1, PS2) genes encode integral transmembrane proteins putatively involved in cell-cell recognition, cell-fate determination, intercellular signaling and Aβ peptide formation. Cyclooxygenase-2 (COX-2), also a membrane-associated oxidoreductase, is a key intermediary in the propagation of neuroinflammation in Alzheimer’s disease (AD).
Rogaev et al. (492.14) examined RNA message abundance for PS1, PS2 and COX-2 in: (a) gerbil hippocampus 72 hr after a single episode of cerebral ischemia; (b) hypoxic rat retina undergoing neovascularization; and (c) human neural cells in primary culture after treatment with Aβ42, NMDA and IL-1B. PS1, PS2 and COX-2 RNA message levels were quantitated, and displayed remarkably parallel induction kinetics (r212 and one to three hrs, respectively. Therefore, PS1 and COX-2 are characteristic of rapidly transduced mRNAs, while the RNA message for PS2 is not. DNA sequence analysis of the TATA-box containing PS1, PS2 and COX-2 promoters exhibited important similarities in their repertoire of transcription factor recognition sites, including those for AP2α, HIF-1 and for the proinflammatory TF triad AP1, NF-KB and STAT1/3. The human PS2 promoter contains six HIF-1 regulatory sites (consensus 5'CGTG-3') and was found to be strongly induced in neovascularization models of retinal hypoxia.
Taken together, the data suggest that the PS1, PS2, and COX-2 genes (1) are developmentally regulated, (2) share coregulated transcriptional control and that (3) expression of the PS1, PS2 and COX-2 genes may be an early neural genetic response to both acute and chronic brain stress. (See also Lukiw et al.)—Walter Lukiw
(Note: Dr. Lukiw is an author of this abstract.)
References: 492.14. Rogaev EI, Lukiw WJ, Colangelo V2, Gordon WC1, Bazan NG2. Coordinated PS1, PS2 and COX-2 gene transcription in oxidation stressed hippocampus, retina and human neural progenitor cells.
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