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Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer's disease mouse models. / Huang, Yunhong; Skwarek-Maruszewska, Aneta; Horré, Katrien; Vandewyer, Elke; Wolfs, Leen; Snellinx, An; Saito, Takashi; Radaelli, Enrico; Corthout, Nikky; Colombelli, Julien; Lo, Adrian C; Van Aerschot, Leen; Callaerts-Vegh, Zsuzsanna; Trabzuni, Daniah; Bossers, Koen; Verhaagen, Joost; Ryten, Mina; Munck, Sebastian; D'Hooge, Rudi; Swaab, Dick F; Hardy, John; Saido, Takaomi C; De Strooper, Bart; Thathiah, Amantha.

In: Science Translational Medicine, Vol. 7, No. 309, 14.10.2015, p. 309ra164.

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Harvard

Huang, Y, Skwarek-Maruszewska, A, Horré, K, Vandewyer, E, Wolfs, L, Snellinx, A, Saito, T, Radaelli, E, Corthout, N, Colombelli, J, Lo, AC, Van Aerschot, L, Callaerts-Vegh, Z, Trabzuni, D, Bossers, K, Verhaagen, J, Ryten, M, Munck, S, D'Hooge, R, Swaab, DF, Hardy, J, Saido, TC, De Strooper, B & Thathiah, A 2015, 'Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer's disease mouse models' Science Translational Medicine, vol. 7, no. 309, pp. 309ra164. DOI: 10.1126/scitranslmed.aab3492

APA

Huang, Y., Skwarek-Maruszewska, A., Horré, K., Vandewyer, E., Wolfs, L., Snellinx, A., ... Thathiah, A. (2015). Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer's disease mouse models. DOI: 10.1126/scitranslmed.aab3492

Vancouver

Huang Y, Skwarek-Maruszewska A, Horré K, Vandewyer E, Wolfs L, Snellinx A et al. Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer's disease mouse models. Science Translational Medicine. 2015 Oct 14;7(309):309ra164. Available from, DOI: 10.1126/scitranslmed.aab3492

Author

Huang, Yunhong ; Skwarek-Maruszewska, Aneta ; Horré, Katrien ; Vandewyer, Elke ; Wolfs, Leen ; Snellinx, An ; Saito, Takashi ; Radaelli, Enrico ; Corthout, Nikky ; Colombelli, Julien ; Lo, Adrian C ; Van Aerschot, Leen ; Callaerts-Vegh, Zsuzsanna ; Trabzuni, Daniah ; Bossers, Koen ; Verhaagen, Joost ; Ryten, Mina ; Munck, Sebastian ; D'Hooge, Rudi ; Swaab, Dick F ; Hardy, John ; Saido, Takaomi C ; De Strooper, Bart ; Thathiah, Amantha. / Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer's disease mouse models. In: Science Translational Medicine. 2015 ; Vol. 7, No. 309. pp. 309ra164

BibTeX

@article{b8c44726f4194ea9924e7cc19d445651,
title = "Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer's disease mouse models",
abstract = "The orphan G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) GPR3 regulates activity of the γ-secretase complex in the absence of an effect on Notch proteolysis, providing a potential therapeutic target for Alzheimer's disease (AD). However, given the vast resources required to develop and evaluate any new therapy for AD and the multiple failures involved in translational research, demonstration of the pathophysiological relevance of research findings in multiple disease-relevant models is necessary before initiating costly drug development programs. We evaluated the physiological consequences of loss of Gpr3 in four AD transgenic mouse models, including two that contain the humanized murine Aβ sequence and express similar amyloid precursor protein (APP) levels as wild-type mice, thereby reducing potential artificial phenotypes. Our findings reveal that genetic deletion of Gpr3 reduced amyloid pathology in all of the AD mouse models and alleviated cognitive deficits in APP/PS1 mice. Additional three-dimensional visualization and analysis of the amyloid plaque burden provided accurate information on the amyloid load, distribution, and volume in the structurally intact adult mouse brain. Analysis of 10 different regions in healthy human postmortem brain tissue indicated that GPR3 expression was stable during aging. However, two cohorts of human AD postmortem brain tissue samples showed a correlation between elevated GPR3 and AD progression. Collectively, these studies provide evidence that GPR3 mediates the amyloidogenic proteolysis of APP in four AD transgenic mouse models as well as the physiological processing of APP in wild-type mice, suggesting that GPR3 may be a potential therapeutic target for AD drug development.",
author = "Yunhong Huang and Aneta Skwarek-Maruszewska and Katrien Horr{\'e} and Elke Vandewyer and Leen Wolfs and An Snellinx and Takashi Saito and Enrico Radaelli and Nikky Corthout and Julien Colombelli and Lo, {Adrian C} and {Van Aerschot}, Leen and Zsuzsanna Callaerts-Vegh and Daniah Trabzuni and Koen Bossers and Joost Verhaagen and Mina Ryten and Sebastian Munck and Rudi D'Hooge and Swaab, {Dick F} and John Hardy and Saido, {Takaomi C} and {De Strooper}, Bart and Amantha Thathiah",
note = "Copyright {\circledC} 2015, American Association for the Advancement of Science.",
year = "2015",
month = "10",
day = "14",
doi = "10.1126/scitranslmed.aab3492",
language = "English",
volume = "7",
pages = "309ra164",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "309",

}

RIS

TY - JOUR

T1 - Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer's disease mouse models

AU - Huang,Yunhong

AU - Skwarek-Maruszewska,Aneta

AU - Horré,Katrien

AU - Vandewyer,Elke

AU - Wolfs,Leen

AU - Snellinx,An

AU - Saito,Takashi

AU - Radaelli,Enrico

AU - Corthout,Nikky

AU - Colombelli,Julien

AU - Lo,Adrian C

AU - Van Aerschot,Leen

AU - Callaerts-Vegh,Zsuzsanna

AU - Trabzuni,Daniah

AU - Bossers,Koen

AU - Verhaagen,Joost

AU - Ryten,Mina

AU - Munck,Sebastian

AU - D'Hooge,Rudi

AU - Swaab,Dick F

AU - Hardy,John

AU - Saido,Takaomi C

AU - De Strooper,Bart

AU - Thathiah,Amantha

N1 - Copyright © 2015, American Association for the Advancement of Science.

PY - 2015/10/14

Y1 - 2015/10/14

N2 - The orphan G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) GPR3 regulates activity of the γ-secretase complex in the absence of an effect on Notch proteolysis, providing a potential therapeutic target for Alzheimer's disease (AD). However, given the vast resources required to develop and evaluate any new therapy for AD and the multiple failures involved in translational research, demonstration of the pathophysiological relevance of research findings in multiple disease-relevant models is necessary before initiating costly drug development programs. We evaluated the physiological consequences of loss of Gpr3 in four AD transgenic mouse models, including two that contain the humanized murine Aβ sequence and express similar amyloid precursor protein (APP) levels as wild-type mice, thereby reducing potential artificial phenotypes. Our findings reveal that genetic deletion of Gpr3 reduced amyloid pathology in all of the AD mouse models and alleviated cognitive deficits in APP/PS1 mice. Additional three-dimensional visualization and analysis of the amyloid plaque burden provided accurate information on the amyloid load, distribution, and volume in the structurally intact adult mouse brain. Analysis of 10 different regions in healthy human postmortem brain tissue indicated that GPR3 expression was stable during aging. However, two cohorts of human AD postmortem brain tissue samples showed a correlation between elevated GPR3 and AD progression. Collectively, these studies provide evidence that GPR3 mediates the amyloidogenic proteolysis of APP in four AD transgenic mouse models as well as the physiological processing of APP in wild-type mice, suggesting that GPR3 may be a potential therapeutic target for AD drug development.

AB - The orphan G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) GPR3 regulates activity of the γ-secretase complex in the absence of an effect on Notch proteolysis, providing a potential therapeutic target for Alzheimer's disease (AD). However, given the vast resources required to develop and evaluate any new therapy for AD and the multiple failures involved in translational research, demonstration of the pathophysiological relevance of research findings in multiple disease-relevant models is necessary before initiating costly drug development programs. We evaluated the physiological consequences of loss of Gpr3 in four AD transgenic mouse models, including two that contain the humanized murine Aβ sequence and express similar amyloid precursor protein (APP) levels as wild-type mice, thereby reducing potential artificial phenotypes. Our findings reveal that genetic deletion of Gpr3 reduced amyloid pathology in all of the AD mouse models and alleviated cognitive deficits in APP/PS1 mice. Additional three-dimensional visualization and analysis of the amyloid plaque burden provided accurate information on the amyloid load, distribution, and volume in the structurally intact adult mouse brain. Analysis of 10 different regions in healthy human postmortem brain tissue indicated that GPR3 expression was stable during aging. However, two cohorts of human AD postmortem brain tissue samples showed a correlation between elevated GPR3 and AD progression. Collectively, these studies provide evidence that GPR3 mediates the amyloidogenic proteolysis of APP in four AD transgenic mouse models as well as the physiological processing of APP in wild-type mice, suggesting that GPR3 may be a potential therapeutic target for AD drug development.

U2 - 10.1126/scitranslmed.aab3492

DO - 10.1126/scitranslmed.aab3492

M3 - Article

VL - 7

SP - 309ra164

JO - Science Translational Medicine

T2 - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 309

ER -

ID: 1544601