Alzheimer's disease-associated amyloid beta interacts with the human serine protease HtrA2/Omi

Hyo Jin Park; Young Mo Seong; Ju Youn Choi; Seongman Kang; Hyangshuk Rhim

doi:10.1016/j.neulet.2003.11.068

Alzheimer's disease-associated amyloid beta interacts with the human serine protease HtrA2/Omi

Hyo Jin Park, Young Mo Seong, Ju Youn Choi, Seongman Kang, Hyangshuk Rhim

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

65 Citations (Scopus)

Abstract

Amyloid beta (Aβ), a principle component of the cerebral plaques found in the brains of patients with Alzheimer's disease (AD), is a pivotal factor implicated in the pathogenesis of AD. Recent reports show that not only extracellular Aβ but also intracellular Aβ induces neuronal apoptosis; however, the mechanism remains to be elucidated. Using yeast two-hybrid assays, we found that Aβ interacts with HtrA2/Omi, an essential human serine protease with proapoptotic activity. Additionally, we mapped the C-terminal region containing the PDZ domain of HtrA2/Omi as the binding determinant for Aβ? The interaction of Aβ with HtrA2/Omi was further confirmed through in vivo co-immunoprecipitation assay in HEK293 cells. This study suggests the possibility that the accumulation of intracellular Aβ and a function of proapoptotic protease, HtrA2/Omi are correlated.

Original language	English
Pages (from-to)	63-67
Number of pages	5
Journal	Neuroscience Letters
Volume	357
Issue number	1
DOIs	https://doi.org/10.1016/j.neulet.2003.11.068
Publication status	Published - 2004 Feb 26

Bibliographical note

Funding Information:
We thank Dr K. Fukuchi for pCXN2 APP and P.S. Edmunds for critical reading of the manuscript. This work was supported by the interdisciplinary research program of KOSEF (1999-2-210-002-5) and Life Phenomena & Function Research Group Program from the Ministry of Science and Technology (M1-0016-00-0032).

Keywords

Alzheimer's disease
Amyloid beta
HtrA2/Omi
PDZ domain

ASJC Scopus subject areas

General Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.neulet.2003.11.068

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title = "Alzheimer's disease-associated amyloid beta interacts with the human serine protease HtrA2/Omi",

abstract = "Amyloid beta (Aβ), a principle component of the cerebral plaques found in the brains of patients with Alzheimer's disease (AD), is a pivotal factor implicated in the pathogenesis of AD. Recent reports show that not only extracellular Aβ but also intracellular Aβ induces neuronal apoptosis; however, the mechanism remains to be elucidated. Using yeast two-hybrid assays, we found that Aβ interacts with HtrA2/Omi, an essential human serine protease with proapoptotic activity. Additionally, we mapped the C-terminal region containing the PDZ domain of HtrA2/Omi as the binding determinant for Aβ? The interaction of Aβ with HtrA2/Omi was further confirmed through in vivo co-immunoprecipitation assay in HEK293 cells. This study suggests the possibility that the accumulation of intracellular Aβ and a function of proapoptotic protease, HtrA2/Omi are correlated.",

keywords = "Alzheimer's disease, Amyloid beta, HtrA2/Omi, PDZ domain",

author = "Park, {Hyo Jin} and Seong, {Young Mo} and Choi, {Ju Youn} and Seongman Kang and Hyangshuk Rhim",

note = "Funding Information: We thank Dr K. Fukuchi for pCXN2 APP and P.S. Edmunds for critical reading of the manuscript. This work was supported by the interdisciplinary research program of KOSEF (1999-2-210-002-5) and Life Phenomena & Function Research Group Program from the Ministry of Science and Technology (M1-0016-00-0032).",

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AU - Park, Hyo Jin

AU - Seong, Young Mo

AU - Choi, Ju Youn

AU - Kang, Seongman

AU - Rhim, Hyangshuk

N1 - Funding Information: We thank Dr K. Fukuchi for pCXN2 APP and P.S. Edmunds for critical reading of the manuscript. This work was supported by the interdisciplinary research program of KOSEF (1999-2-210-002-5) and Life Phenomena & Function Research Group Program from the Ministry of Science and Technology (M1-0016-00-0032).

PY - 2004/2/26

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N2 - Amyloid beta (Aβ), a principle component of the cerebral plaques found in the brains of patients with Alzheimer's disease (AD), is a pivotal factor implicated in the pathogenesis of AD. Recent reports show that not only extracellular Aβ but also intracellular Aβ induces neuronal apoptosis; however, the mechanism remains to be elucidated. Using yeast two-hybrid assays, we found that Aβ interacts with HtrA2/Omi, an essential human serine protease with proapoptotic activity. Additionally, we mapped the C-terminal region containing the PDZ domain of HtrA2/Omi as the binding determinant for Aβ? The interaction of Aβ with HtrA2/Omi was further confirmed through in vivo co-immunoprecipitation assay in HEK293 cells. This study suggests the possibility that the accumulation of intracellular Aβ and a function of proapoptotic protease, HtrA2/Omi are correlated.

AB - Amyloid beta (Aβ), a principle component of the cerebral plaques found in the brains of patients with Alzheimer's disease (AD), is a pivotal factor implicated in the pathogenesis of AD. Recent reports show that not only extracellular Aβ but also intracellular Aβ induces neuronal apoptosis; however, the mechanism remains to be elucidated. Using yeast two-hybrid assays, we found that Aβ interacts with HtrA2/Omi, an essential human serine protease with proapoptotic activity. Additionally, we mapped the C-terminal region containing the PDZ domain of HtrA2/Omi as the binding determinant for Aβ? The interaction of Aβ with HtrA2/Omi was further confirmed through in vivo co-immunoprecipitation assay in HEK293 cells. This study suggests the possibility that the accumulation of intracellular Aβ and a function of proapoptotic protease, HtrA2/Omi are correlated.

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Alzheimer's disease-associated amyloid beta interacts with the human serine protease HtrA2/Omi

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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