CA150 expression delays striatal cell death in overexpression and knock-in conditions for mutant huntingtin neurotoxicity.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Margarita ArangoChristian Néri

Abstract

Transcriptional dysregulation caused by expanded polyglutamines (polyGlns) in huntingtin (htt) may be central to cell-autonomous mechanisms for neuronal cell death in Huntington's disease (HD) pathogenesis. We hypothesized that these mechanisms may involve the dysfunction of the transcriptional regulator CA150, a putative modifier of onset age in HD, because it binds to htt and accumulates in an HD grade-dependent manner in striatal and cortical neurons. Consistently, we report herein that CA150 expression rescues striatal cell death in lentiviral overexpression (rats) and knock-in (mouse cells) conditions for mutant htt neurotoxicity. In both systems, rescue was dependent on the (Gln-Ala)38 repeat normally found in CA150. We excluded the possibility that rescue may be caused by the (Gln-Ala)38 repeat interacting with polyGlns and, by doing so, blocking mutant htt toxicity. In contrast, we found the (Gln-Ala)38 repeat is required for the nuclear restriction of exogenous CA150, suggesting that rescue requires nuclear CA150. Additionally, we found the (Gln-Ala)38 repeat was dispensable for CA150 transcriptional repression ability, suggesting further that CA150 localization is critical to rescue. Finally, rescue was associated wit...Continue Reading

Citations

Sep 5, 2012·Molecular Neurobiology·Pawel M SwitonskiMaciej Figiel
Mar 22, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Valérie PerrinNicole Déglon
Mar 31, 2012·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Lina YinByron C Jones
Feb 28, 2009·PloS One·Elsa DiguetEmmanuel Brouillet
Sep 8, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·J Alex ParkerChristian Neri
Oct 25, 2006·Proceedings of the National Academy of Sciences of the United States of America·Neil FergusonAlan R Fersht
Sep 24, 2008·Revue neurologique·E RozeJ Caboche
Oct 24, 2015·Wiley Interdisciplinary Reviews. RNA·Soraya BecerraCarlos Suñé
Dec 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Leslie RipaudMark S Hipp
Aug 13, 2015·Journal of Cellular Biochemistry·Nicholas J MillerWilliam J Roesler
Dec 12, 2012·Trends in Cell Biology·Elyse S BlumShai Shaham
Apr 28, 2012·Gene·Marta MontesCarlos Suñé
Feb 7, 2012·Journal of Molecular Biology·Ronald Wetzel
Sep 6, 2011·Neurobiology of Disease·Marta Ruiz, Nicole Déglon
Dec 18, 2007·Molecular and Cellular Neurosciences·Kadiombo BantubungiSerge N Schiffmann
Mar 7, 2007·Trends in Neurosciences·Laura ConfortiMichael P Coleman
Jun 11, 2011·Journal of Peptide Science : an Official Publication of the European Peptide Society·Zerrin FidanRudolf Volkmer
Jul 11, 2012·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Susan Shur-Fen GauChia-Hsiang Chen
Nov 8, 2013·Journal of Biomolecular Screening·Jonathan BardIgnacio Munoz-Sanjuan
Mar 11, 2010·The Journal of Biological Chemistry·Miguel Sánchez-ÁlvarezCarlos Suñé
Jul 9, 2008·Current Opinion in Neurology·Emmanuel RozeJocelyne Caboche
May 10, 2008·The Biochemical Journal·Sara ImarisioDavid C Rubinsztein
Jan 12, 2008·The Journal of Biological Chemistry·James L PearsonMariano A Garcia-Blanco
Dec 14, 2018·Acta Neuropathologica Communications·Marine PonsMagalie Lecourtois
Feb 9, 2017·Biochemistry·Adewale AdegbuyiroJustin Legleiter

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.