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Assessment of normal and mutant human presenilin function in Caenorhabditis elegans

By Diane Levitan, Timothy G. Doyle, Denise Brousseau, Michael K. Lee, Gopal Thinakaran, Hilda H. Slunt, Sangram S. Sisodia and Iva Greenwald

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

Topics: Biological Sciences
Publisher: The National Academy of Sciences of the USA
Year: 1996
OAI identifier: oai:pubmedcentral.nih.gov:26241
Provided by: PubMed Central
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