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

Leticia Pérez-Sisqués; Júlia Solana-Balaguer; Genís Campoy-Campos; Núria Martín-Flores; Anna Sancho-Balsells; Marcel Vives-Isern; Ferran Soler-Palazón; Marta Garcia-Forn; Mercè Masana; Jordi Alberch; Esther Pérez Navarro; Albert Giralt; Cristina Malagelada

doi:10.20944/preprints202111.0393.v1

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preprints.org > biology and life sciences > biochemistry and molecular biology > doi: 10.20944/preprints202111.0393.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Leticia Pérez-Sisqués

Júlia Solana-Balaguer

^* ,

Version 1 : Received: 18 November 2021 / Approved: 22 November 2021 / Online: 22 November 2021 (13:11:49 CET)

A peer-reviewed article of this Preprint also exists.

Pérez-Sisqués, L.; Solana-Balaguer, J.; Campoy-Campos, G.; Martín-Flores, N.; Sancho-Balsells, A.; Vives-Isern, M.; Soler-Palazón, F.; Garcia-Forn, M.; Masana, M.; Alberch, J.; Pérez-Navarro, E.; Giralt, A.; Malagelada, C. RTP801/REDD1 Is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington’s Disease. Biomolecules 2022, 12, 34. Pérez-Sisqués, L.; Solana-Balaguer, J.; Campoy-Campos, G.; Martín-Flores, N.; Sancho-Balsells, A.; Vives-Isern, M.; Soler-Palazón, F.; Garcia-Forn, M.; Masana, M.; Alberch, J.; Pérez-Navarro, E.; Giralt, A.; Malagelada, C. RTP801/REDD1 Is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington’s Disease. Biomolecules 2022, 12, 34.

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 of 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.

Keywords

RTP801/REDD1; Huntington’s disease; neuroinflammation; hippocampus; cognitive dysfunction.

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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