Implications of the serine protease HtrA1 in amyloid precursor protein processing

Sandra Grau; Alfonso Baldi; Rossana Bussani; Xiaodan Tian; Raluca Stefanescu; Michael Przybylski; Peter Richards; Simon A. Jones; Viji Shridhar; Tim Clausen; Michael Ehrmann

doi:10.1073/pnas.0501823102

Implications of the serine protease HtrA1 in amyloid precursor protein processing

Sandra Grau, Alfonso Baldi, Rossana Bussani, Xiaodan Tian, Raluca Stefanescu, Michael Przybylski, Peter Richards, Simon A. Jones, Viji Shridhar, Tim Clausen, Michael Ehrmann

Laboratory Medicine and Pathology

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

139 Scopus citations

Abstract

The defining features of the widely conserved HtrA (high temperature requirement) family of serine proteases are the combination of a catalytic protease domain with one or more C-terminal PDZ domains and reversible zymogen activation. Even though HtrAs have previously been implicated in protein quality control and various diseases, including cancer, arthritis, and neuromuscular disorder, the biology of the human family members is not well understood. Our data suggest that HtrA1 is directly involved in the β-amyloid pathway as it degrades various fragments of amyloid precursor protein while an HtrA1 inhibitor causes accumulation of Aβ in astrocyte cell culture supernatants. Furthermore, HtrA1 colocalizes with β-amyloid deposits in human brain samples. Potential implications in Alzheimer's disease are discussed.

Original language	English (US)
Pages (from-to)	6021-6026
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	102
Issue number	17
DOIs	https://doi.org/10.1073/pnas.0501823102
State	Published - Apr 26 2005

Keywords

Amyloid β
C99
Protein quality control

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.0501823102

Cite this

Grau, S., Baldi, A., Bussani, R., Tian, X., Stefanescu, R., Przybylski, M., Richards, P., Jones, S. A., Shridhar, V., Clausen, T., & Ehrmann, M. (2005). Implications of the serine protease HtrA1 in amyloid precursor protein processing. Proceedings of the National Academy of Sciences of the United States of America, 102(17), 6021-6026. https://doi.org/10.1073/pnas.0501823102

Grau, S, Baldi, A, Bussani, R, Tian, X, Stefanescu, R, Przybylski, M, Richards, P, Jones, SA, Shridhar, V, Clausen, T & Ehrmann, M 2005, 'Implications of the serine protease HtrA1 in amyloid precursor protein processing', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 17, pp. 6021-6026. https://doi.org/10.1073/pnas.0501823102

@article{e4b416f046794dbc9702d56149d74753,

title = "Implications of the serine protease HtrA1 in amyloid precursor protein processing",

abstract = "The defining features of the widely conserved HtrA (high temperature requirement) family of serine proteases are the combination of a catalytic protease domain with one or more C-terminal PDZ domains and reversible zymogen activation. Even though HtrAs have previously been implicated in protein quality control and various diseases, including cancer, arthritis, and neuromuscular disorder, the biology of the human family members is not well understood. Our data suggest that HtrA1 is directly involved in the β-amyloid pathway as it degrades various fragments of amyloid precursor protein while an HtrA1 inhibitor causes accumulation of Aβ in astrocyte cell culture supernatants. Furthermore, HtrA1 colocalizes with β-amyloid deposits in human brain samples. Potential implications in Alzheimer's disease are discussed.",

keywords = "Amyloid β, C99, Protein quality control",

author = "Sandra Grau and Alfonso Baldi and Rossana Bussani and Xiaodan Tian and Raluca Stefanescu and Michael Przybylski and Peter Richards and Jones, {Simon A.} and Viji Shridhar and Tim Clausen and Michael Ehrmann",

year = "2005",

month = apr,

day = "26",

doi = "10.1073/pnas.0501823102",

language = "English (US)",

volume = "102",

pages = "6021--6026",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "17",

}

TY - JOUR

T1 - Implications of the serine protease HtrA1 in amyloid precursor protein processing

AU - Grau, Sandra

AU - Baldi, Alfonso

AU - Bussani, Rossana

AU - Tian, Xiaodan

AU - Stefanescu, Raluca

AU - Przybylski, Michael

AU - Richards, Peter

AU - Jones, Simon A.

AU - Shridhar, Viji

AU - Clausen, Tim

AU - Ehrmann, Michael

PY - 2005/4/26

Y1 - 2005/4/26

N2 - The defining features of the widely conserved HtrA (high temperature requirement) family of serine proteases are the combination of a catalytic protease domain with one or more C-terminal PDZ domains and reversible zymogen activation. Even though HtrAs have previously been implicated in protein quality control and various diseases, including cancer, arthritis, and neuromuscular disorder, the biology of the human family members is not well understood. Our data suggest that HtrA1 is directly involved in the β-amyloid pathway as it degrades various fragments of amyloid precursor protein while an HtrA1 inhibitor causes accumulation of Aβ in astrocyte cell culture supernatants. Furthermore, HtrA1 colocalizes with β-amyloid deposits in human brain samples. Potential implications in Alzheimer's disease are discussed.

AB - The defining features of the widely conserved HtrA (high temperature requirement) family of serine proteases are the combination of a catalytic protease domain with one or more C-terminal PDZ domains and reversible zymogen activation. Even though HtrAs have previously been implicated in protein quality control and various diseases, including cancer, arthritis, and neuromuscular disorder, the biology of the human family members is not well understood. Our data suggest that HtrA1 is directly involved in the β-amyloid pathway as it degrades various fragments of amyloid precursor protein while an HtrA1 inhibitor causes accumulation of Aβ in astrocyte cell culture supernatants. Furthermore, HtrA1 colocalizes with β-amyloid deposits in human brain samples. Potential implications in Alzheimer's disease are discussed.

KW - Amyloid β

KW - C99

KW - Protein quality control

UR - http://www.scopus.com/inward/record.url?scp=20944444077&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20944444077&partnerID=8YFLogxK

U2 - 10.1073/pnas.0501823102

DO - 10.1073/pnas.0501823102

M3 - Article

C2 - 15855271

AN - SCOPUS:20944444077

SN - 0027-8424

VL - 102

SP - 6021

EP - 6026

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 17

ER -

Implications of the serine protease HtrA1 in amyloid precursor protein processing

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this