Detection of the presenilin 1 COOH-terminal fragment in the extracellular compartment: A release enhanced by apoptosis

Luisa Benussi, Antonella Alberici, Manuel Mayhaus, Uwe Langer, Roberta Ghidoni, Federica Mazzoli, Francesca Nicosia, Laura Barbiero, Giovanni Frisoni, Orazio Zanetti, Laura Gasparini, Roger M. Nitsch, Giuliano Binetti

Research output: Contribution to journalArticle

Abstract

Mutations in gene encoding presenilin 1 (PS1) are responsible for the majority of familial Alzheimer's disease (FAD) cases. We studied PS1 localization in HEK293 cells and in primary neurons obtained from rat cortex and hippocampus. We first demonstrated that PS1-CTF, but neither PS1-FL nor PS1-NTF, is released into the medium as a soluble and membrane-associated form. After induction of apoptosis with staurosporine (Sts), we observed a dramatic increase in the level of PS1-CTF in the medium, both in HEK293 and in primary neurons. Immunocytochemical analysis suggested that the release of PS1-CTF might occur via membrane shedding. Aβ1-42 treatment reduced PS1-CTF extracellular levels. This decrease was strongly associated to an impaired secretion of sAPP fragments, thus suggesting a role of PS1-CTF in the control of trafficking and generation of APP fragments.

Original languageEnglish
Pages (from-to)256-265
Number of pages10
JournalExperimental Cell Research
Volume269
Issue number2
DOIs
Publication statusPublished - Oct 1 2001

Keywords

  • Alzheimer disease
  • Apoptosis
  • Presenilin 1
  • Primary neuronal cultures
  • Shedding

ASJC Scopus subject areas

  • Cell Biology

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