Cell Biology

Life Without Amyloid

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Science  16 Feb 2007:
Vol. 315, Issue 5814, pp. 914
DOI: 10.1126/science.315.5814.914c

The amyloid precursor protein (APP) is a trans-membrane protein that has been linked to some forms of familial Alzheimer's disease, but the normal function of the protein is a mystery. The nematode worm Caenorhabditis elegans possesses a single APP-related gene, termed apl-1. Hornsten et al. have examined the role of apl-1, which is expressed in a variety of tissues, including neurons. Worms with a disrupted apl-1 gene died as larvae, exhibiting defects in molting, locomotion, and morphogenesis. These mutants could be rescued by the expression of the soluble extracellular domain of APL-1 protein in neurons. In addition, over-expressing the APL-1 protein in a wild-type background was detrimental; this effect could be mitigated by reducing the levels of SEL-12, which is a C. elegans homolog of presenilin, an enzyme that cleaves APP in humans. Thus, it appears that APL-1 performs an essential function during development in the nervous system. Interfering with APP expression or modifications in patients may therefore have unintended and unexpected consequences. — SMH

Proc. Natl. Acad. Sci. U.S.A. 104, 1971 (2007).

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