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Potential roles for presenilin-1 in oxygen sensing and in glial-specific gene expression

The integral membrane glycoprotein presenilin-1 (PS1), in concert with &bgr;-secretase and beta amyloid precursor protein (&bgr;APP), orchestrate cleavage of &bgr;APP into amyloidogenic A&bgr; peptides. To gain further insight into PS1 function, we undertook a gene expression profiling study that interrogated the expression of 12 000 genes in the forebrain of PS1-hypomorphic mice that exhibit highly attenuated PS1 activity. Using stringent RNA screening, DNA array and Northern assay, we report significant down-regulation in the expression of &bgr;APP and hypoxia inducible factor-1 alpha (HIF-1&agr;), and a marked up-regulation in the expression of glial-specific markers that include S100&bgr; protein, glycerol phosphate dehydrogenase, and glial fibrillary acidic protein. These data suggest potential roles for PS1 in the cellular response to hypoxia and glial-specific gene expression.