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Title: Rtp801/redd1 is involved in neuroinflammation and modulates cognitive dysfunction in huntingtons disease
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 Nadal, Mercè
Alberch i Vié, Jordi
Pérez Navarro, Esther
Giralt Torroella, Albert
Malagelada Grau, Cristina
Keywords: Corea de Huntington
Huntington's chorea
Issue Date: 27-Dec-2021
Publisher: MDPI
Abstract: 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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It is part of: Biomolecules, 2022, vol. 12, num. 1, p. 34
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ISSN: 2218-273X
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Biomedicina)

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