A novel specific PERK activator reduces toxicity and extends survival in Huntington's disease models.

Animals Apoptosis / drug effects Disease Models, Animal Endoplasmic Reticulum Stress / drug effects Enzyme Activators / chemistry Eukaryotic Initiation Factor-2 / metabolism Huntingtin Protein / metabolism Huntington Disease / enzymology Mice Models, Biological Neostriatum / pathology Neurons / drug effects Neuroprotective Agents / pharmacology Phosphorylation / drug effects Signal Transduction / drug effects Survival Analysis eIF-2 Kinase / metabolism

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
23 04 2020
Historique:
received: 22 09 2019
accepted: 02 04 2020
entrez: 25 4 2020
pubmed: 25 4 2020
medline: 1 12 2020
Statut: epublish

Résumé

One of the pathways of the unfolded protein response, initiated by PKR-like endoplasmic reticulum kinase (PERK), is key to neuronal homeostasis in neurodegenerative diseases. PERK pathway activation is usually accomplished by inhibiting eIF2α-P dephosphorylation, after its phosphorylation by PERK. Less tried is an approach involving direct PERK activation without compromising long-term recovery of eIF2α function by dephosphorylation. Here we show major improvement in cellular (STHdh

Identifiants

DOI: 10.1038/s41598-020-63899-4 PMID: 32327686 PMC: PMC7181660
pubmed: 32327686
doi: 10.1038/s41598-020-63899-4
pii: 10.1038/s41598-020-63899-4
pmc: PMC7181660
doi:

Substances chimiques

Enzyme Activators 0
Eukaryotic Initiation Factor-2 0
Htt protein, mouse 0
Huntingtin Protein 0
Neuroprotective Agents 0
PERK kinase EC 2.7.11.1
eIF-2 Kinase EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6875

Références

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Auteurs

Javier Ganz (J)

Department of Human Molecular Genetics and Biochemistry, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 69978, Israel.
ORCID: 0000-0002-2370-9819

Talya Shacham (T)

Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 69978, Israel.
School of Molecular Cell Biology and Biotechnology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.

Maria Kramer (M)

School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.

Marina Shenkman (M)

Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 69978, Israel.
School of Molecular Cell Biology and Biotechnology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.

Hagit Eiger (H)

Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 69978, Israel.
School of Molecular Cell Biology and Biotechnology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.

Nitai Weinberg (N)

Department of Human Molecular Genetics and Biochemistry, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 69978, Israel.

Ori Iancovici (O)

Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 69978, Israel.
School of Molecular Cell Biology and Biotechnology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.

Somnath Roy (S)

Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 69978, Israel.
School of Molecular Cell Biology and Biotechnology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.

Luba Simhaev (L)

Blavatnik Center for Drug Discovery, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.

Benny Da'adoosh (B)

Blavatnik Center for Drug Discovery, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.

Hamutal Engel (H)

Blavatnik Center for Drug Discovery, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.

Nisim Perets (N)

Department of Human Molecular Genetics and Biochemistry, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 69978, Israel.

Yael Barhum (Y)

Department of Human Molecular Genetics and Biochemistry, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 69978, Israel.

Moshe Portnoy (M)

School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.

Daniel Offen (D)

Department of Human Molecular Genetics and Biochemistry, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 69978, Israel.

Gerardo Z Lederkremer (GZ)

Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 69978, Israel. gerardol@tauex.tau.ac.il.
School of Molecular Cell Biology and Biotechnology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel. gerardol@tauex.tau.ac.il.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › A novel specific PERK activator reduces...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › A novel specific PERK activator reduces...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › A novel specific PERK activator reduces...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Stress du réticulum endoplasmique › A novel specific PERK activator reduces...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Activateurs d'enzymes › A novel specific PERK activator reduces...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines ribosomiques › Facteurs initiation chaîne peptidique › Facteurs d'initiation eucaryotes › Facteur-2 d'initiation eucaryote › A novel specific PERK activator reduces...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéine huntingtine › A novel specific PERK activator reduces...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie de Huntington › A novel specific PERK activator reduces...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › A novel specific PERK activator reduces...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › A novel specific PERK activator reduces...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Noyaux gris centraux › Corps strié › Néostriatum › A novel specific PERK activator reduces...
questionsmedicales.fr › Cellules › Neurones › A novel specific PERK activator reduces...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Neuroprotecteurs › A novel specific PERK activator reduces...
questionsmedicales.fr › Métabolisme › Phosphorylation › A novel specific PERK activator reduces...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › A novel specific PERK activator reduces...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › A novel specific PERK activator reduces...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › eIF-2 Kinase › A novel specific PERK activator reduces...