Processing of the amyloid protein precursor to potentially amyloidogenic derivatives

Todd E. Golde, Steven Estus, Linda H. Younkin, Dennis J. Selkoe, Steven G. Younkin

Research output: Contribution to journalArticle

606 Scopus citations

Abstract

The ∼120-kilodalton amyloid β proton precursor (βAPP) is processed into a complex set of 8- to 12-kilodalton carboxyl-terminal derivatives that includes potentially amyloidogenic forms with the ∼4-kilodalton amyloid β protein (βAP) at or near their amino terminus. In order to determine if these derivatives are processed in a secretory pathway or by the endosomal-lysosomal system, (i) deletion mutants that produce the normal set of carboxyl-terminal derivatives and shortened secreted derivatives were analyzed and (ii) the effect of inhibitors of endosomal-lysosomal processing was examined. In the secretory pathway, cleavage of the βAPP occurs at a single site within the βAP to generate one secreted derivative and one nonamyloidogenic carboxyl-terminal fragment, whereas, in the endosomal-lysosomal system, a complex set of carboxyl-terminal derivatives is produced that includes the potentially amyloidogenic forms.

Original languageEnglish (US)
Pages (from-to)728-730
Number of pages3
JournalScience
Volume255
Issue number5045
DOIs
StatePublished - Jan 1 1992

ASJC Scopus subject areas

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