Homer2 and Homer3 interact with amyloid precursor protein and inhibit Aβ production

Loukia Parisiadou, Ioanna Bethani, Vasiliki Michaki, Kaliopi Krousti, Georgia Rapti, Spiros Efthimiopoulos*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The study of Amyloid Precursor Protein (APP) processing has been the focus of considerable interest, since it leads to Aβ peptide generation, the main constituent of neuritic plaques found in brains of Alzheimer's disease patients. Therefore, the identification of novel APP binding partners that regulate Aβ peptide production represents a pharmaceutical target aiming at reducing Αβ pathology. In this study, we provide evidence that Homer2 and Homer3 but not Homer1 proteins interact specifically with APP. Their expression inhibits APP processing and reduces secretion of Aβ peptides. In addition, they decrease the levels of cell surface APP and inhibit maturation of APP and β-secretase (BACE1). The effects of Homer2 and Homer3 on APP trafficking to the cell surface and/or on APP and BACE1 maturation could be part of the mechanism by which the expression of these proteins leads to the significant reduction of Aβ peptide production.

Original languageEnglish (US)
Pages (from-to)353-364
Number of pages12
JournalNeurobiology of Disease
Volume30
Issue number3
DOIs
StatePublished - Jun 1 2008

Keywords

  • Alzheimer
  • Amyloid
  • Neurodegeneration
  • Secretase

ASJC Scopus subject areas

  • Neurology

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