AβPP intracellular C-terminal domain function is related to its degradation processes

Erica Buoso, Fabrizio Biundo, Cristina Lanni, Gennaro Schettini, Stefano Govoni, Marco Racchi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The amyloid-β protein precursor (AβPP) can be processed by either the amyloidogenic or the non-amyloidogenic pathway; both pathways lead to release of the AβPP intracellular C-terminal domain (AICD). AICD involvement in signal transduction within Fe65/Tip60 complex is one of the most discussed mechanisms, and different models have been hypothesized to explain the role of AICD within this complex. The analysis of these models in relation to the degradation processes highlights the discrepancy among AICD localization, function, and degradation, leading to the hypothesis that a signaling mechanism may exist which allows AβPP proteolysis to generate either a transcriptionally active fragment or an inactive one with different involvement of proteasome and IDE (insulin-degrading enzyme). Our work aimed to analyze the functional role of AICD within the Fe65/Tip60 complex considering the AICD degradation processes. Our data suggest a correlation between the role of AICD in gene regulation and its removal operated by proteasome activity. Moreover, treatments with IDE inhibitor underlined the presence of an alternative mechanism involved in AICD removal when the latter is not exerting nuclear activity, thus providing clearer support for the existence of at least two mechanisms as previously suggested.

Original languageEnglish (US)
Pages (from-to)393-405
Number of pages13
JournalJournal of Alzheimer's Disease
Volume30
Issue number2
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Fingerprint

Amyloid beta-Protein Precursor
Insulysin
Proteasome Endopeptidase Complex
Enzyme Inhibitors
Proteolysis
Signal Transduction
Genes

Keywords

  • AICD
  • AβPP
  • Fe65
  • IDE
  • proteasome
  • Tip60

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

AβPP intracellular C-terminal domain function is related to its degradation processes. / Buoso, Erica; Biundo, Fabrizio; Lanni, Cristina; Schettini, Gennaro; Govoni, Stefano; Racchi, Marco.

In: Journal of Alzheimer's Disease, Vol. 30, No. 2, 01.01.2012, p. 393-405.

Research output: Contribution to journalArticle

Buoso, Erica ; Biundo, Fabrizio ; Lanni, Cristina ; Schettini, Gennaro ; Govoni, Stefano ; Racchi, Marco. / AβPP intracellular C-terminal domain function is related to its degradation processes. In: Journal of Alzheimer's Disease. 2012 ; Vol. 30, No. 2. pp. 393-405.
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