Pharmacological Inhibition of the VCP/Proteasome Axis Rescues Photoreceptor Degeneration in RHOP23H Rat Retinal Explants
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Título: | Pharmacological Inhibition of the VCP/Proteasome Axis Rescues Photoreceptor Degeneration in RHOP23H Rat Retinal Explants |
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Autor/es: | Sen, Merve | Kutsyr, Oksana | Cao, Bowen | Bolz, Sylvia | Arango-Gonzalez, Blanca | Ueffing, Marius |
Grupo/s de investigación o GITE: | Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS) |
Centro, Departamento o Servicio: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología |
Palabras clave: | Ocular therapy | Ocular disease | Retinal organotypic culture | Retinal degeneration | Retinitis pigmentosa | RHOP23H |
Área/s de conocimiento: | Biología Celular |
Fecha de publicación: | 16-oct-2021 |
Editor: | MDPI |
Cita bibliográfica: | Sen M, Kutsyr O, Cao B, Bolz S, Arango-Gonzalez B, Ueffing M. Pharmacological Inhibition of the VCP/Proteasome Axis Rescues Photoreceptor Degeneration in RHOP23H Rat Retinal Explants. Biomolecules. 2021; 11(10):1528. https://doi.org/10.3390/biom11101528 |
Resumen: | Rhodopsin (RHO) misfolding mutations are a common cause of the blinding disease autosomal dominant retinitis pigmentosa (adRP). The most prevalent mutation, RHOP23H, results in its misfolding and retention in the endoplasmic reticulum (ER). Under homeostatic conditions, misfolded proteins are selectively identified, retained at the ER, and cleared via ER-associated degradation (ERAD). Overload of these degradation processes for a prolonged period leads to imbalanced proteostasis and may eventually result in cell death. ERAD of misfolded proteins, such as RHOP23H, includes the subsequent steps of protein recognition, targeting for ERAD, retrotranslocation, and proteasomal degradation. In the present study, we investigated and compared pharmacological modulation of ERAD at these four different major steps. We show that inhibition of the VCP/proteasome activity favors cell survival and suppresses P23H-mediated retinal degeneration in RHOP23H rat retinal explants. We suggest targeting this activity as a therapeutic approach for patients with currently untreatable adRP. |
Patrocinador/es: | This study was supported by funds (to M.U. and B.A-G) from FFB (Grant PPA-0717-0719-RAD), the Kerstan Foundation, European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie (Grant agreement No. 722717—project OCUTHER), the ProRetina Foundation, the Maloch Stiftung, and the Open Access Publishing Fund of University of Tübingen. |
URI: | http://hdl.handle.net/10045/118919 |
ISSN: | 2218-273X |
DOI: | 10.3390/biom11101528 |
Idioma: | eng |
Tipo: | info:eu-repo/semantics/article |
Derechos: | © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
Revisión científica: | si |
Versión del editor: | https://doi.org/10.3390/biom11101528 |
Aparece en las colecciones: | INV - NEUROVIS - Artículos de Revistas Investigaciones financiadas por la UE |
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