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

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

doi:10.1016/j.nbd.2008.02.004

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

Pharmacology

Research output: Contribution to journal › Article › peer-review

33 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 language	English (US)
Pages (from-to)	353-364
Number of pages	12
Journal	Neurobiology of Disease
Volume	30
Issue number	3
DOIs	https://doi.org/10.1016/j.nbd.2008.02.004
State	Published - Jun 2008

Funding

This research was funded by grants from the Greek General Secretariat for Research and Technology (PENED), the Ministry of Education (Pythagoras I and II), the University of Athens (Kapodistrias), European Union (APOPIS, Contract No.LSHM-CT-2003-503330) and Embeirikeion foundation.

Keywords

Alzheimer
Amyloid
Neurodegeneration
Secretase

ASJC Scopus subject areas

Neurology

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title = "Homer2 and Homer3 interact with amyloid precursor protein and inhibit Aβ production",

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.",

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author = "Loukia Parisiadou and Ioanna Bethani and Vasiliki Michaki and Kaliopi Krousti and Georgia Rapti and Spiros Efthimiopoulos",

note = "Funding Information: This research was funded by grants from the Greek General Secretariat for Research and Technology (PENED), the Ministry of Education (Pythagoras I and II), the University of Athens (Kapodistrias), European Union (APOPIS, Contract No.LSHM-CT-2003-503330) and Embeirikeion foundation.",

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AU - Bethani, Ioanna

AU - Michaki, Vasiliki

AU - Krousti, Kaliopi

AU - Rapti, Georgia

AU - Efthimiopoulos, Spiros

N1 - Funding Information: This research was funded by grants from the Greek General Secretariat for Research and Technology (PENED), the Ministry of Education (Pythagoras I and II), the University of Athens (Kapodistrias), European Union (APOPIS, Contract No.LSHM-CT-2003-503330) and Embeirikeion foundation.

PY - 2008/6

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N2 - 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.

AB - 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.

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KW - Neurodegeneration

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

Abstract

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Keywords

ASJC Scopus subject areas

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