1. CA150 rescues striatal cell death in overexpression and knock-in models of Huntington's disease
- Author
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Arango, M., Holbert, Sébastien, Zala, D., Brouillet, E., Regulier, E., Thakur, A. Kumar, Aebischer, P, Wetzel, R., Deglon, N., Neri, C., Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole Polytechnique Fédérale de Lausanne (EPFL), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Tennessee, and ProdInra, Migration
- Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,nervous system ,biomarker ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,transcription ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,pathogenic mechanisms - Abstract
Session : Pathogenic mechanisms II; International audience; Huntington’s disease (HD) is a dominant neurodegenerative disorder associated with N-terminal expanded polyglutamines (polyGlns) in huntingtin (htt). The abnormal regulation of transcription may be central to HD neuronal pathology. We previously reported that the transcriptional regulator CA150 binds to htt and accumulates in a neuropathological grade dependent manner in the striatal and cortical neurons of HD patients, suggesting CA150 dysfunction in HD. Consistently, we report herein that CA150 overexpression rescued the toxicity of mutant htt in lentiviral overexpression (rat striatum) and knock-in (striatal cells from HdhQ111 mice) models of HD. In both systems, the rescue was dependent on the presence of the (Gln-Ala)38 repeat normally found in CA150. Our data indicate that the striatal pathology in HD may involve a loss of CA150 function. Additionally, our data provide a biological rationale for the previously reported influence of the enlarged and potentially hypomorphic repeat alleles on the age at onset in HD
- Published
- 2005