Protective role of Engrailed in a Drosophila model of Huntington's disease

Human Molecular Genetics
Bruno MugatFlorence Maschat

Abstract

Huntington's disease (HD) is caused by the expansion of the polyglutamine (polyQ) tract in the human Huntingtin (hHtt) protein (polyQ-hHtt). Although this mutation behaves dominantly, htt loss of function may also contribute to HD pathogenesis. Using a Drosophila model of HD, we found that Engrailed (EN), a transcriptional activator of endogenous Drosophila htt (dhtt), is able to prevent aggregation of polyQ-hHtt. To interpret these findings, we tested and identified a protective role of N-terminal fragments of both Drosophila and Human wild-type Htt onto polyQ-hHtt-induced cellular defects. In addition, N-terminal parts of normal hHtt were also able to rescue eye degeneration due to the loss of Drosophila endogenous dhtt function. Thus, our data indicate that Drosophila and Human Htt share biological properties, and confirm a model whereby EN activates endogenous dhtt, which in turn prevents polyQ-hHtt-induced phenotypes. The protective role of wild-type hHtt N-terminal parts, specifically onto polyQ-hHtt-induced cellular toxicity suggests that the HD may be considered as a dominant negative disease rather than solely dominant.

References

Mar 12, 1987·Nature·N S WexlerM A Ramos Arroyo
Feb 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·T Kornberg
Mar 21, 1998·Human Molecular Genetics·S EngelenderC A Ross
Jul 3, 1998·The EMBO Journal·N Serrano, F Maschat
Aug 11, 1999·Human Molecular Genetics·Z LiR M Myers
Jan 3, 2001·American Journal of Human Genetics·B R LeavittM R Hayden
Aug 17, 2001·Trends in Neurosciences·P Aebischer, J Ridet
Mar 5, 2003·Brain : a Journal of Neurology·Ferdinando SquitieriStefano Di Donato
Feb 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Wyan-Ching Mimi LeeJ Troy Littleton
Mar 24, 2004·Trends in Genetics : TIG·Shi-Hua Li, Xiao-Jiang Li
Jul 30, 2004·Developmental Biology·Grégory ChanasFlorence Maschat
Sep 2, 2004·Molecular and Cellular Biology·Eugenia TrushinaCynthia T McMurray
Oct 8, 2004·The EMBO Journal·Carina I HolmbergRichard I Morimoto
Nov 4, 2005·Nature·Isabelle BrunetChristine Holt
Nov 17, 2005·Nature Reviews. Neuroscience·Elena CattaneoMarzia Tartari
Oct 24, 2006·Behavioural Brain Research·Barbara KuemerleKarl Herrup
Nov 28, 2006·Developmental Biology·Willy JolyFlorence Maschat
Feb 3, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Laure SonnierAlain Prochiantz

❮ Previous
Next ❯

Citations

Apr 18, 2009·Apoptosis : an International Journal on Programmed Cell Death·Bingwei Lu
Oct 5, 2010·PLoS Currents·Erin Gonzales, Jerry Yin
Jul 19, 2013·PloS One·Yoan ArribatFlorence Maschat
Mar 18, 2016·Orphanet Journal of Rare Diseases·Cecilia Marelli, Florence Maschat
Aug 6, 2014·Acta Neuropathologica Communications·Yoan ArribatFlorence Maschat
Jun 4, 2018·Human Molecular Genetics·Simon CoulyFlorence Maschat
Apr 14, 2021·CNS & Neurological Disorders Drug Targets·Iqra Subhan, Yasir Hasan Siddique

❮ 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.