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RTP801/REDD1 Is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington’s Disease

RTP801/REDD1 is a stress-regulated protein whose levels are increased in several neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and Huntington’s diseases (HD). RTP801 downregulation ameliorates behavioral abnormalities in several mouse models of these disorders. In HD, RTP801 mediates...

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Autores principales: Pérez-Sisqués, Leticia, Solana-Balaguer, Júlia, Campoy-Campos, Genís, Martín-Flores, Núria, Sancho-Balsells, Anna, Vives-Isern, Marcel, Soler-Palazón, Ferran, Garcia-Forn, Marta, Masana, Mercè, Alberch, Jordi, Pérez-Navarro, Esther, Giralt, Albert, Malagelada, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773874/
https://www.ncbi.nlm.nih.gov/pubmed/35053183
http://dx.doi.org/10.3390/biom12010034
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author Pérez-Sisqués, Leticia
Solana-Balaguer, Júlia
Campoy-Campos, Genís
Martín-Flores, Núria
Sancho-Balsells, Anna
Vives-Isern, Marcel
Soler-Palazón, Ferran
Garcia-Forn, Marta
Masana, Mercè
Alberch, Jordi
Pérez-Navarro, Esther
Giralt, Albert
Malagelada, Cristina
author_facet Pérez-Sisqués, Leticia
Solana-Balaguer, Júlia
Campoy-Campos, Genís
Martín-Flores, Núria
Sancho-Balsells, Anna
Vives-Isern, Marcel
Soler-Palazón, Ferran
Garcia-Forn, Marta
Masana, Mercè
Alberch, Jordi
Pérez-Navarro, Esther
Giralt, Albert
Malagelada, Cristina
author_sort Pérez-Sisqués, Leticia
collection PubMed
description RTP801/REDD1 is a stress-regulated protein whose levels are increased in several neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and Huntington’s diseases (HD). RTP801 downregulation ameliorates behavioral abnormalities in several mouse models of these disorders. In HD, RTP801 mediates mutant huntingtin (mhtt) toxicity in in vitro models and its levels are increased in human iPSCs, human postmortem putamen samples, and in striatal synaptosomes from mouse models of the disease. Here, we investigated the role of RTP801 in the hippocampal pathophysiology of HD. We found that RTP801 levels are increased in the hippocampus of HD patients in correlation with gliosis markers. Although RTP801 expression is not altered in the hippocampus of the R6/1 mouse model of HD, neuronal RTP801 silencing in the dorsal hippocampus with shRNA containing AAV particles ameliorates cognitive alterations. This recovery is associated with a partial rescue of synaptic markers and with a reduction in inflammatory events, especially microgliosis. Altogether, our results indicate that RTP801 could be a marker of hippocampal neuroinflammation in HD patients and a promising therapeutic target of the disease.
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spelling pubmed-87738742022-01-21 RTP801/REDD1 Is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington’s Disease Pérez-Sisqués, Leticia Solana-Balaguer, Júlia Campoy-Campos, Genís Martín-Flores, Núria Sancho-Balsells, Anna Vives-Isern, Marcel Soler-Palazón, Ferran Garcia-Forn, Marta Masana, Mercè Alberch, Jordi Pérez-Navarro, Esther Giralt, Albert Malagelada, Cristina Biomolecules Article RTP801/REDD1 is a stress-regulated protein whose levels are increased in several neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and Huntington’s diseases (HD). RTP801 downregulation ameliorates behavioral abnormalities in several mouse models of these disorders. In HD, RTP801 mediates mutant huntingtin (mhtt) toxicity in in vitro models and its levels are increased in human iPSCs, human postmortem putamen samples, and in striatal synaptosomes from mouse models of the disease. Here, we investigated the role of RTP801 in the hippocampal pathophysiology of HD. We found that RTP801 levels are increased in the hippocampus of HD patients in correlation with gliosis markers. Although RTP801 expression is not altered in the hippocampus of the R6/1 mouse model of HD, neuronal RTP801 silencing in the dorsal hippocampus with shRNA containing AAV particles ameliorates cognitive alterations. This recovery is associated with a partial rescue of synaptic markers and with a reduction in inflammatory events, especially microgliosis. Altogether, our results indicate that RTP801 could be a marker of hippocampal neuroinflammation in HD patients and a promising therapeutic target of the disease. MDPI 2021-12-27 /pmc/articles/PMC8773874/ /pubmed/35053183 http://dx.doi.org/10.3390/biom12010034 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Pérez-Sisqués, Leticia
Solana-Balaguer, Júlia
Campoy-Campos, Genís
Martín-Flores, Núria
Sancho-Balsells, Anna
Vives-Isern, Marcel
Soler-Palazón, Ferran
Garcia-Forn, Marta
Masana, Mercè
Alberch, Jordi
Pérez-Navarro, Esther
Giralt, Albert
Malagelada, Cristina
RTP801/REDD1 Is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington’s Disease
title RTP801/REDD1 Is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington’s Disease
title_full RTP801/REDD1 Is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington’s Disease
title_fullStr RTP801/REDD1 Is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington’s Disease
title_full_unstemmed RTP801/REDD1 Is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington’s Disease
title_short RTP801/REDD1 Is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington’s Disease
title_sort rtp801/redd1 is involved in neuroinflammation and modulates cognitive dysfunction in huntington’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773874/
https://www.ncbi.nlm.nih.gov/pubmed/35053183
http://dx.doi.org/10.3390/biom12010034
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