Pharmacological modulation of the ER stress response ameliorates oculopharyngeal muscular dystrophy. / Malerba, Alberto; Roth, Fanny; Harish, Pradeep; Dhiab, Jamila; Lu-Nguyen, Ngoc; Cappellari, Ornella; Jarmin, Susan; Mahoudeau, Alexandrine; Ythier, Victor; Laine, Jeanne; Negroni, Elisa; Abgueguen, Emmanuelle; Simonelig, Martine; Guedat, Philippe; Mouly, Vincent; Butler-Browne, Gillian; Voisset, Cecile; Dickson, George; Trollet, Capucine.

In: Human Molecular Genetics, Vol. 28, No. 10, ddz007, 15.05.2019, p. 1694-1708.

Research output: Contribution to journalArticle

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Pharmacological modulation of the ER stress response ameliorates oculopharyngeal muscular dystrophy. / Malerba, Alberto; Roth, Fanny; Harish, Pradeep; Dhiab, Jamila; Lu-Nguyen, Ngoc; Cappellari, Ornella; Jarmin, Susan; Mahoudeau, Alexandrine; Ythier, Victor; Laine, Jeanne; Negroni, Elisa; Abgueguen, Emmanuelle; Simonelig, Martine; Guedat, Philippe; Mouly, Vincent; Butler-Browne, Gillian; Voisset, Cecile; Dickson, George; Trollet, Capucine.

In: Human Molecular Genetics, Vol. 28, No. 10, ddz007, 15.05.2019, p. 1694-1708.

Research output: Contribution to journalArticle

Harvard

Malerba, A, Roth, F, Harish, P, Dhiab, J, Lu-Nguyen, N, Cappellari, O, Jarmin, S, Mahoudeau, A, Ythier, V, Laine, J, Negroni, E, Abgueguen, E, Simonelig, M, Guedat, P, Mouly, V, Butler-Browne, G, Voisset, C, Dickson, G & Trollet, C 2019, 'Pharmacological modulation of the ER stress response ameliorates oculopharyngeal muscular dystrophy', Human Molecular Genetics, vol. 28, no. 10, ddz007, pp. 1694-1708. https://doi.org/10.1093/hmg/ddz007

APA

Malerba, A., Roth, F., Harish, P., Dhiab, J., Lu-Nguyen, N., Cappellari, O., ... Trollet, C. (2019). Pharmacological modulation of the ER stress response ameliorates oculopharyngeal muscular dystrophy. Human Molecular Genetics, 28(10), 1694-1708. [ddz007]. https://doi.org/10.1093/hmg/ddz007

Vancouver

Author

Malerba, Alberto ; Roth, Fanny ; Harish, Pradeep ; Dhiab, Jamila ; Lu-Nguyen, Ngoc ; Cappellari, Ornella ; Jarmin, Susan ; Mahoudeau, Alexandrine ; Ythier, Victor ; Laine, Jeanne ; Negroni, Elisa ; Abgueguen, Emmanuelle ; Simonelig, Martine ; Guedat, Philippe ; Mouly, Vincent ; Butler-Browne, Gillian ; Voisset, Cecile ; Dickson, George ; Trollet, Capucine. / Pharmacological modulation of the ER stress response ameliorates oculopharyngeal muscular dystrophy. In: Human Molecular Genetics. 2019 ; Vol. 28, No. 10. pp. 1694-1708.

BibTeX

@article{b5956cec7f97478b8e74daa3d5eb8a9b,
title = "Pharmacological modulation of the ER stress response ameliorates oculopharyngeal muscular dystrophy",
abstract = "Oculopharyngeal muscular dystrophy (OPMD) is a rare late onset genetic disease leading to ptosis, dysphagia, and proximal limb muscles at later stages. A short abnormal (GCN) triplet expansion in the polyA-binding protein nuclear 1 (PABPN1) gene leads to PABPN1-containing aggregates in the muscles of OPMD patients. Here we demonstrate that treating mice with guanabenz acetate (GA), an FDA-approved antihypertensive drug, reduces the size and number of nuclear aggregates, improves muscle force, protects myofibers from the pathology-derived turnover and decreases fibrosis. GA targets various cell processes, including the unfolded protein response (UPR), which acts to attenuate endoplasmic reticulum (ER) stress. We demonstrate that GA increases both the phosphorylation of the eukaryotic translation initiator factor 2α subunit (eIF2α) and the splicing of Xbp1, key components of the UPR. Altogether these data show that modulation of protein folding regulation is beneficial for OPMD and promote the further development of GA or its derivatives for treatment of OPMD in humans. Furthermore, they support the recent evidences that treating ER stress could be therapeutically relevant in other more common proteinopathies.",
author = "Alberto Malerba and Fanny Roth and Pradeep Harish and Jamila Dhiab and Ngoc Lu-Nguyen and Ornella Cappellari and Susan Jarmin and Alexandrine Mahoudeau and Victor Ythier and Jeanne Laine and Elisa Negroni and Emmanuelle Abgueguen and Martine Simonelig and Philippe Guedat and Vincent Mouly and Gillian Butler-Browne and Cecile Voisset and George Dickson and Capucine Trollet",
year = "2019",
month = "5",
day = "15",
doi = "10.1093/hmg/ddz007",
language = "English",
volume = "28",
pages = "1694--1708",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "10",

}

RIS

TY - JOUR

T1 - Pharmacological modulation of the ER stress response ameliorates oculopharyngeal muscular dystrophy

AU - Malerba, Alberto

AU - Roth, Fanny

AU - Harish, Pradeep

AU - Dhiab, Jamila

AU - Lu-Nguyen, Ngoc

AU - Cappellari, Ornella

AU - Jarmin, Susan

AU - Mahoudeau, Alexandrine

AU - Ythier, Victor

AU - Laine, Jeanne

AU - Negroni, Elisa

AU - Abgueguen, Emmanuelle

AU - Simonelig, Martine

AU - Guedat, Philippe

AU - Mouly, Vincent

AU - Butler-Browne, Gillian

AU - Voisset, Cecile

AU - Dickson, George

AU - Trollet, Capucine

PY - 2019/5/15

Y1 - 2019/5/15

N2 - Oculopharyngeal muscular dystrophy (OPMD) is a rare late onset genetic disease leading to ptosis, dysphagia, and proximal limb muscles at later stages. A short abnormal (GCN) triplet expansion in the polyA-binding protein nuclear 1 (PABPN1) gene leads to PABPN1-containing aggregates in the muscles of OPMD patients. Here we demonstrate that treating mice with guanabenz acetate (GA), an FDA-approved antihypertensive drug, reduces the size and number of nuclear aggregates, improves muscle force, protects myofibers from the pathology-derived turnover and decreases fibrosis. GA targets various cell processes, including the unfolded protein response (UPR), which acts to attenuate endoplasmic reticulum (ER) stress. We demonstrate that GA increases both the phosphorylation of the eukaryotic translation initiator factor 2α subunit (eIF2α) and the splicing of Xbp1, key components of the UPR. Altogether these data show that modulation of protein folding regulation is beneficial for OPMD and promote the further development of GA or its derivatives for treatment of OPMD in humans. Furthermore, they support the recent evidences that treating ER stress could be therapeutically relevant in other more common proteinopathies.

AB - Oculopharyngeal muscular dystrophy (OPMD) is a rare late onset genetic disease leading to ptosis, dysphagia, and proximal limb muscles at later stages. A short abnormal (GCN) triplet expansion in the polyA-binding protein nuclear 1 (PABPN1) gene leads to PABPN1-containing aggregates in the muscles of OPMD patients. Here we demonstrate that treating mice with guanabenz acetate (GA), an FDA-approved antihypertensive drug, reduces the size and number of nuclear aggregates, improves muscle force, protects myofibers from the pathology-derived turnover and decreases fibrosis. GA targets various cell processes, including the unfolded protein response (UPR), which acts to attenuate endoplasmic reticulum (ER) stress. We demonstrate that GA increases both the phosphorylation of the eukaryotic translation initiator factor 2α subunit (eIF2α) and the splicing of Xbp1, key components of the UPR. Altogether these data show that modulation of protein folding regulation is beneficial for OPMD and promote the further development of GA or its derivatives for treatment of OPMD in humans. Furthermore, they support the recent evidences that treating ER stress could be therapeutically relevant in other more common proteinopathies.

U2 - 10.1093/hmg/ddz007

DO - 10.1093/hmg/ddz007

M3 - Article

VL - 28

SP - 1694

EP - 1708

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 10

M1 - ddz007

ER -