Caspase cleaved presenilin-1 is part of active gamma-secretase complexes

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Standard

Caspase cleaved presenilin-1 is part of active gamma-secretase complexes. / Hansson, Camilla A; Popescu, Bogdan O; Laudon, Hanna; Cedazo-Minguez, Angel; Popescu, Laurentiu M; Winblad, Bengt; Ankarcrona, Maria; Petersen, Anna Camilla Hansson.

In: Journal of Neurochemistry, Vol. 97, No. 2, 2006, p. 356-64.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hansson, CA, Popescu, BO, Laudon, H, Cedazo-Minguez, A, Popescu, LM, Winblad, B, Ankarcrona, M & Petersen, ACH 2006, 'Caspase cleaved presenilin-1 is part of active gamma-secretase complexes', Journal of Neurochemistry, vol. 97, no. 2, pp. 356-64. https://doi.org/10.1111/j.1471-4159.2006.03735.x

APA

Hansson, C. A., Popescu, B. O., Laudon, H., Cedazo-Minguez, A., Popescu, L. M., Winblad, B., Ankarcrona, M., & Petersen, A. C. H. (2006). Caspase cleaved presenilin-1 is part of active gamma-secretase complexes. Journal of Neurochemistry, 97(2), 356-64. https://doi.org/10.1111/j.1471-4159.2006.03735.x

Vancouver

Hansson CA, Popescu BO, Laudon H, Cedazo-Minguez A, Popescu LM, Winblad B et al. Caspase cleaved presenilin-1 is part of active gamma-secretase complexes. Journal of Neurochemistry. 2006;97(2):356-64. https://doi.org/10.1111/j.1471-4159.2006.03735.x

Author

Hansson, Camilla A ; Popescu, Bogdan O ; Laudon, Hanna ; Cedazo-Minguez, Angel ; Popescu, Laurentiu M ; Winblad, Bengt ; Ankarcrona, Maria ; Petersen, Anna Camilla Hansson. / Caspase cleaved presenilin-1 is part of active gamma-secretase complexes. In: Journal of Neurochemistry. 2006 ; Vol. 97, No. 2. pp. 356-64.

Bibtex

@article{98dbee12081b470dbf07e1cddee65dca,
title = "Caspase cleaved presenilin-1 is part of active gamma-secretase complexes",
abstract = "gamma-Secretase is a key enzyme involved in the processing of the beta-amyloid precursor protein into amyloid beta-peptides (Abeta). Abeta accumulates and forms plaques in Alzheimer's disease (AD) brains. A progressive neurodegeneration and cognitive decline occurs during the course of the disease, and Abeta is believed to be central for the molecular pathogenesis of AD. Apoptosis has been implicated as one of the mechanisms behind the neuronal cell loss seen in AD. We have studied preservation and activity of the gamma-secretase complex during apoptosis in neuroblastoma cells (SH-SY5Y) exposed to staurosporine (STS). We report that the known components (presenilin, Nicastrin, Aph-1 and Pen-2) interact and form active gamma-secretase complexes in apoptotic cells. In addition, the fragments corresponding to the PS1 N-terminal fragment and the caspase-cleaved PS1 C-terminal fragment (PS1-caspCTF) were found to form active gamma-secretase complexes when co-expressed in presenilin (PS) knockout cells. Interestingly, PS1-caspCTF replaced the normal PS1 C-terminal fragment and was co-immunoprecipitated with the gamma-secretase complex in SH-SY5Y cells exposed to STS. In addition, Abeta was detected in medium from apoptotic HEK APP(swe) cells. Together, the data show that gamma-secretase complexes containing PS1-caspCTF are active, and suggest that this proteolytic activity is also important in dying cells and may affect the progression of AD.",
keywords = "Amyloid Precursor Protein Secretases, Amyloid beta-Protein Precursor, Apoptosis, Aspartic Acid Endopeptidases, Blotting, Western, Caspases, Cell Line, Tumor, Cell Survival, Chromatin, Endopeptidases, Enzyme Activation, Enzyme Inhibitors, Humans, Immunoprecipitation, Luciferases, Membrane Proteins, Multiprotein Complexes, Mutation, Neuroblastoma, Peptide Fragments, Presenilin-1, Protein Structure, Tertiary, Staurosporine, Subcellular Fractions, Tetrazolium Salts, Thiazoles, Transfection",
author = "Hansson, {Camilla A} and Popescu, {Bogdan O} and Hanna Laudon and Angel Cedazo-Minguez and Popescu, {Laurentiu M} and Bengt Winblad and Maria Ankarcrona and Petersen, {Anna Camilla Hansson}",
year = "2006",
doi = "10.1111/j.1471-4159.2006.03735.x",
language = "English",
volume = "97",
pages = "356--64",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "2",

}

RIS

TY - JOUR

T1 - Caspase cleaved presenilin-1 is part of active gamma-secretase complexes

AU - Hansson, Camilla A

AU - Popescu, Bogdan O

AU - Laudon, Hanna

AU - Cedazo-Minguez, Angel

AU - Popescu, Laurentiu M

AU - Winblad, Bengt

AU - Ankarcrona, Maria

AU - Petersen, Anna Camilla Hansson

PY - 2006

Y1 - 2006

N2 - gamma-Secretase is a key enzyme involved in the processing of the beta-amyloid precursor protein into amyloid beta-peptides (Abeta). Abeta accumulates and forms plaques in Alzheimer's disease (AD) brains. A progressive neurodegeneration and cognitive decline occurs during the course of the disease, and Abeta is believed to be central for the molecular pathogenesis of AD. Apoptosis has been implicated as one of the mechanisms behind the neuronal cell loss seen in AD. We have studied preservation and activity of the gamma-secretase complex during apoptosis in neuroblastoma cells (SH-SY5Y) exposed to staurosporine (STS). We report that the known components (presenilin, Nicastrin, Aph-1 and Pen-2) interact and form active gamma-secretase complexes in apoptotic cells. In addition, the fragments corresponding to the PS1 N-terminal fragment and the caspase-cleaved PS1 C-terminal fragment (PS1-caspCTF) were found to form active gamma-secretase complexes when co-expressed in presenilin (PS) knockout cells. Interestingly, PS1-caspCTF replaced the normal PS1 C-terminal fragment and was co-immunoprecipitated with the gamma-secretase complex in SH-SY5Y cells exposed to STS. In addition, Abeta was detected in medium from apoptotic HEK APP(swe) cells. Together, the data show that gamma-secretase complexes containing PS1-caspCTF are active, and suggest that this proteolytic activity is also important in dying cells and may affect the progression of AD.

AB - gamma-Secretase is a key enzyme involved in the processing of the beta-amyloid precursor protein into amyloid beta-peptides (Abeta). Abeta accumulates and forms plaques in Alzheimer's disease (AD) brains. A progressive neurodegeneration and cognitive decline occurs during the course of the disease, and Abeta is believed to be central for the molecular pathogenesis of AD. Apoptosis has been implicated as one of the mechanisms behind the neuronal cell loss seen in AD. We have studied preservation and activity of the gamma-secretase complex during apoptosis in neuroblastoma cells (SH-SY5Y) exposed to staurosporine (STS). We report that the known components (presenilin, Nicastrin, Aph-1 and Pen-2) interact and form active gamma-secretase complexes in apoptotic cells. In addition, the fragments corresponding to the PS1 N-terminal fragment and the caspase-cleaved PS1 C-terminal fragment (PS1-caspCTF) were found to form active gamma-secretase complexes when co-expressed in presenilin (PS) knockout cells. Interestingly, PS1-caspCTF replaced the normal PS1 C-terminal fragment and was co-immunoprecipitated with the gamma-secretase complex in SH-SY5Y cells exposed to STS. In addition, Abeta was detected in medium from apoptotic HEK APP(swe) cells. Together, the data show that gamma-secretase complexes containing PS1-caspCTF are active, and suggest that this proteolytic activity is also important in dying cells and may affect the progression of AD.

KW - Amyloid Precursor Protein Secretases

KW - Amyloid beta-Protein Precursor

KW - Apoptosis

KW - Aspartic Acid Endopeptidases

KW - Blotting, Western

KW - Caspases

KW - Cell Line, Tumor

KW - Cell Survival

KW - Chromatin

KW - Endopeptidases

KW - Enzyme Activation

KW - Enzyme Inhibitors

KW - Humans

KW - Immunoprecipitation

KW - Luciferases

KW - Membrane Proteins

KW - Multiprotein Complexes

KW - Mutation

KW - Neuroblastoma

KW - Peptide Fragments

KW - Presenilin-1

KW - Protein Structure, Tertiary

KW - Staurosporine

KW - Subcellular Fractions

KW - Tetrazolium Salts

KW - Thiazoles

KW - Transfection

U2 - 10.1111/j.1471-4159.2006.03735.x

DO - 10.1111/j.1471-4159.2006.03735.x

M3 - Journal article

C2 - 16539675

VL - 97

SP - 356

EP - 364

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 2

ER -

ID: 41992240