Metformin inhibits RAN translation through PKR pathway and mitigates disease in

Amyotrophic Lateral Sclerosis / metabolism Animals Brain / metabolism C9orf72 Protein / genetics Disease Models, Animal Frontotemporal Dementia / metabolism Humans Metformin / pharmacology Mice Mice, Transgenic Microsatellite Repeats / genetics Protein Biosynthesis / drug effects eIF-2 Kinase / genetics
ALS/FTD C9orf72 PKR RAN translation metformin

Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
04 08 2020
Historique:
pubmed: 22 7 2020
medline: 22 9 2020
entrez: 22 7 2020
Statut: ppublish

Résumé

Repeat associated non-AUG (RAN) translation is found in a growing number of microsatellite expansion diseases, but the mechanisms remain unclear. We show that RAN translation is highly regulated by the double-stranded RNA-dependent protein kinase (PKR). In cells, structured CAG, CCUG, CAGG, and G

Identifiants

DOI: 10.1073/pnas.2005748117 PMID: 32690681 PMC: PMC7414156
pubmed: 32690681
pii: 2005748117
doi: 10.1073/pnas.2005748117
pmc: PMC7414156
doi:

Substances chimiques

C9orf72 Protein 0
Metformin 9100L32L2N
eIF-2 Kinase EC 2.7.11.1

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

18591-18599

Subventions

Organisme : NINDS NIH HHS
ID : R37 NS040389
Pays : United States
Organisme : NINDS NIH HHS
ID : P01 NS058901
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 the Author(s). Published by PNAS.

Déclaration de conflit d'intérêts

Competing interest statement: T.Z., L.N., and L.P.W.R. are listed as inventors on patents filed by the University of Florida related to RAN translation.

Références

Annu Rev Med. 2019 Jan 27;70:167-181
pubmed: 30365357
Curr Opin Genet Dev. 2017 Jun;44:125-134
pubmed: 28365506
Cell. 2010 Feb 5;140(3):338-48
pubmed: 20144759
Nat Med. 2017 Jun;23(6):674-677
pubmed: 28504725
J Pharmacol Exp Ther. 2009 Mar;328(3):866-72
pubmed: 19066342
Nat Commun. 2017 Dec 8;8(1):2005
pubmed: 29222490
Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):260-5
pubmed: 21173221
J Neurochem. 2016 Aug;138 Suppl 1:145-62
pubmed: 27016280
Nature. 2016 Nov 10;539(7628):197-206
pubmed: 27830784
Cell Metab. 2016 Jun 14;23(6):1060-1065
pubmed: 27304507
Cancer Prev Res (Phila). 2010 Sep;3(9):1066-76
pubmed: 20810672
Elife. 2018 Sep 04;7:
pubmed: 30179155
J Cell Biol. 1999 Dec 27;147(7):1431-42
pubmed: 10613902
JAMA Neurol. 2015 Aug;72(8):905-11
pubmed: 26030836
PLoS One. 2011;6(9):e24189
pubmed: 21909419
Front Cell Neurosci. 2017 Apr 11;11:97
pubmed: 28442996
Nat Genet. 2006 Jul;38(7):758-69
pubmed: 16804541
Neuron. 2016 May 4;90(3):521-34
pubmed: 27112499
Cell. 1989 Jan 27;56(2):303-12
pubmed: 2536299
Mol Ther. 2015 Jan;23(1):53-62
pubmed: 25228069
Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):E4968-77
pubmed: 24248382
Cell. 2009 Feb 20;136(4):731-45
pubmed: 19239892
Mol Cell. 2005 Nov 11;20(3):483-9
pubmed: 16285929
Proc Natl Acad Sci U S A. 1994 May 24;91(11):4713-7
pubmed: 7515177
Neuron. 2020 Feb 19;105(4):645-662.e11
pubmed: 31831332
EMBO J. 1997 Feb 3;16(3):611-24
pubmed: 9034343
PLoS Genet. 2012;8(2):e1002481
pubmed: 22383888
Neurosci Lett. 2007 Jan 10;411(2):98-103
pubmed: 17110029
Neuron. 2013 Feb 20;77(4):639-46
pubmed: 23415312
Trends Mol Med. 2018 Jun;24(6):575-589
pubmed: 29716790
Neuron. 2015 Nov 18;88(4):667-77
pubmed: 26590344
Science. 2019 Nov 15;366(6467):843-849
pubmed: 31727829
Cell. 2011 Dec 9;147(6):1384-96
pubmed: 22153080
Methods. 1997 Apr;11(4):361-70
pubmed: 9126551
Brain. 2018 Oct 1;141(10):2855-2865
pubmed: 30169600
Nat Commun. 2018 Jan 4;9(1):51
pubmed: 29302060
Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3907-12
pubmed: 19237574
Cell Metab. 2014 Dec 2;20(6):953-66
pubmed: 25456737
PLoS One. 2017 Jun 20;12(6):e0179283
pubmed: 28632780
Neurochem Int. 2005 Jan;46(1):11-8
pubmed: 15567511
Science. 2013 Mar 15;339(6125):1335-8
pubmed: 23393093
RNA. 2000 Jan;6(1):79-87
pubmed: 10668800
J Biol Chem. 2004 Oct 1;279(40):41715-26
pubmed: 15292165
Eur J Neurol. 2010 May;17(5):733-9
pubmed: 20074230

Auteurs

Tao Zu (T)

Center for NeuroGenetics, College of Medicine, University of Florida, Gainesville, FL 32610.
Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610.
Genetics Institute, University of Florida, Gainesville, FL 32610.

Shu Guo (S)

Center for NeuroGenetics, College of Medicine, University of Florida, Gainesville, FL 32610.
Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610.
Genetics Institute, University of Florida, Gainesville, FL 32610.

Olgert Bardhi (O)

Center for NeuroGenetics, College of Medicine, University of Florida, Gainesville, FL 32610.
Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610.
Genetics Institute, University of Florida, Gainesville, FL 32610.

Daniel A Ryskamp (DA)

Center for NeuroGenetics, College of Medicine, University of Florida, Gainesville, FL 32610.
Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610.
Genetics Institute, University of Florida, Gainesville, FL 32610.
ORCID: 0000-0002-2197-0730

Jian Li (J)

Center for NeuroGenetics, College of Medicine, University of Florida, Gainesville, FL 32610.
Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610.
Genetics Institute, University of Florida, Gainesville, FL 32610.

Solaleh Khoramian Tusi (S)

Center for NeuroGenetics, College of Medicine, University of Florida, Gainesville, FL 32610.
Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610.
Genetics Institute, University of Florida, Gainesville, FL 32610.

Avery Engelbrecht (A)

Center for NeuroGenetics, College of Medicine, University of Florida, Gainesville, FL 32610.
Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610.
Genetics Institute, University of Florida, Gainesville, FL 32610.

Kelena Klippel (K)

Center for NeuroGenetics, College of Medicine, University of Florida, Gainesville, FL 32610.
Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610.
Genetics Institute, University of Florida, Gainesville, FL 32610.

Paramita Chakrabarty (P)

Center for Translation Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32610.
Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610.

Lien Nguyen (L)

Center for NeuroGenetics, College of Medicine, University of Florida, Gainesville, FL 32610.
Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610.
Genetics Institute, University of Florida, Gainesville, FL 32610.

Todd E Golde (TE)

Center for Translation Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32610.
Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610.
McKnight Brain Institute, University of Florida, Gainesville, FL 32610.

Nahum Sonenberg (N)

Department of Biochemistry, McGill University, Montreal, A3A 1A3, Canada; nahum.sonenberg@mcgill.ca ranum@ufl.edu.
ORCID: 0000-0002-4707-8759

Laura P W Ranum (LPW)

Center for NeuroGenetics, College of Medicine, University of Florida, Gainesville, FL 32610; nahum.sonenberg@mcgill.ca ranum@ufl.edu.
Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610.
Genetics Institute, University of Florida, Gainesville, FL 32610.
McKnight Brain Institute, University of Florida, Gainesville, FL 32610.
Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610.
Norman Fixel Institute for Neurological Disease, University of Florida, Gainesville, FL 32608.
ORCID: 0000-0001-9808-9661

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Troubles de l'homéostasie des protéines › Protéinopathies TDP-43 › Sclérose latérale amyotrophique › Metformin inhibits RAN translation through PKR...
questionsmedicales.fr › Eucaryotes › Animaux › Metformin inhibits RAN translation through PKR...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Metformin inhibits RAN translation through PKR...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Régulateurs des protéines G › Facteurs d'échange de nucléotides guanyliques › Protéine C9orf72 › Metformin inhibits RAN translation through PKR...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Metformin inhibits RAN translation through PKR...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Dégénérescence lobaire frontotemporale › Démence frontotemporale › Metformin inhibits RAN translation through PKR...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Metformin inhibits RAN translation through PKR...
questionsmedicales.fr › Composés chimiques organiques › Amidines › Guanidines › Biguanides › Metformine › Metformin inhibits RAN translation through PKR...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Metformin inhibits RAN translation through PKR...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Metformin inhibits RAN translation through PKR...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Séquences répétées en tandem › Répétitions microsatellites › Metformin inhibits RAN translation through PKR...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Biosynthèse des protéines › Metformin inhibits RAN translation through PKR...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › eIF-2 Kinase › Metformin inhibits RAN translation through PKR...