Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/184428
Title: RTP801 is involved in mutant huntingtin-induced cell death
Author: Martín Flores, Núria
Romaní Aumedes, Joan
Rué Cabré, Laura
Canal de la Iglesia, Mercè
Sanders, Phil
Straccia, Marco
Allen, Nicholas D.
Alberch i Vié, Jordi, 1959-
Canals i Coll, Josep M.
Pérez Navarro, Esther
Malagelada Grau, Cristina
Keywords: Proteïnes
Neurones
Mort
Cervell
Malalties neurodegeneratives
Proteins
Neurons
Death
Brain
Neurodegenerative Diseases
Issue Date: Jul-2016
Publisher: Humana Press.
Abstract: RTP801 expression is induced by cellular stress and has a pro-apoptotic function in non-proliferating differentiated cells such as neurons. In several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease, elevated levels of RTP801 have been observed, which suggests a role for RTP801 in neuronal death. Neuronal death is also a pathological hallmark in Huntington's disease (HD), an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Currently, the exact mechanisms underlying mutant huntingtin (mhtt)-induced toxicity are still unclear. Here, we investigated whether RTP801 is involved in (mhtt)-induced cell death. Ectopic exon-1 mhtt elevated RTP801 mRNA and protein levels in nerve growth factor (NGF)-differentiated PC12 cells and in rat primary cortical neurons. In neuronal PC12 cells, mhtt also contributed to RTP801 protein elevation by reducing its proteasomal degradation rate, in addition to promoting RTP801 gene expression. Interestingly, silencing RTP801 expression with short hairpin RNAs (shRNAs) blocked mhtt-induced cell death in NGF-differentiated PC12 cells. However, RTP801 protein levels were not altered in the striatum of Hdh(Q7/Q111) and R6/1 mice, two HD models that display motor deficits but not neuronal death. Importantly, RTP801 protein levels were elevated in both neural telencephalic progenitors differentiated from HD patient-derived induced pluripotent stem cells and in the putamen and cerebellum of human HD postmortem brains. Taken together, our results suggest that RTP801 is a novel downstream effector of mhtt-induced toxicity and that it may be relevant to the human disease.
Note: Versió postprint del document publicat a: https://doi.org/10.1007/s12035-015-9166-6
It is part of: Molecular Neurobiology, 2016, vol. 53, num. 5, p. 2857-2868
URI: http://hdl.handle.net/2445/184428
Related resource: https://doi.org/10.1007/s12035-015-9166-6
ISSN: 0893-7648
Appears in Collections:Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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