Assessment of normal and mutant human presenilin function in Caenorhabditis elegans.

Abstract:

:We provide evidence that normal human presenilins can substitute for Caenorhabditis elegans SEL-12 protein in functional assays in vivo. In addition, six familial Alzheimer disease-linked mutant human presenilins were tested and found to have reduced ability to rescue the sel-12 mutant phenotype, suggesting that they have lower than normal presenilin activity. A human presenilin 1 deletion variant that fails to be proteolytically processed and a mutant SEL-12 protein that lacks the C terminus display considerable activity in this assay, suggesting that neither presenilin proteolysis nor the C terminus is absolutely required for normal presenilin function. We also show that sel-12 is expressed in most neural and nonneural cell types in all developmental stages. The reduced activity of mutant presenilins and as yet unknown gain-of-function properties may be a contributing factor in the development of Alzheimer disease.

authors

Levitan D,Doyle TG,Brousseau D,Lee MK,Thinakaran G,Slunt HH,Sisodia SS,Greenwald I

doi

10.1073/pnas.93.25.14940

subject

Has Abstract

pub_date

1996-12-10 00:00:00

pages

14940-4

issue

25

eissn

0027-8424

issn

1091-6490

journal_volume

93

pub_type

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