Enhanced neuronal glucose transporter expression reveals metabolic choice in a HD Drosophila model

PloS One
Marie Thérèse BessonJean-Charles Liévens

Abstract

Huntington's disease is a neurodegenerative disorder caused by toxic insertions of polyglutamine residues in the Huntingtin protein and characterized by progressive deterioration of cognitive and motor functions. Altered brain glucose metabolism has long been suggested and a possible link has been proposed in HD. However, the precise function of glucose transporters was not yet determined. Here, we report the effects of the specifically-neuronal human glucose transporter expression in neurons of a Drosophila model carrying the exon 1 of the human huntingtin gene with 93 glutamine repeats (HQ93). We demonstrated that overexpression of the human glucose transporter in neurons ameliorated significantly the status of HD flies by increasing their lifespan, reducing their locomotor deficits and rescuing eye neurodegeneration. Then, we investigated whether increasing the major pathways of glucose catabolism, glycolysis and pentose-phosphate pathway (PPP) impacts HD. To mimic increased glycolytic flux, we overexpressed phosphofructokinase (PFK) which catalyzes an irreversible step in glycolysis. Overexpression of PFK did not affect HQ93 fly survival, but protected from photoreceptor loss. Overexpression of glucose-6-phosphate dehydroge...Continue Reading

References

Jan 31, 1992·Biochemical and Biophysical Research Communications·F MaherI A Simpson
Oct 1, 1990·Brain : a Journal of Neurology·T KuwertL E Feinendegen
Oct 1, 1994·Journal of Neurochemistry·W C Gamberino, W A Brennan
Jan 1, 1994·Journal of Neurochemistry·S J Vannucci
Sep 25, 1997·Journal of Neuroscience Research·R L LeinoL R Drewes
Oct 26, 2001·Free Radical Biology & Medicine·S N RadyukW C Orr
May 15, 2002·Brain Research. Molecular Brain Research·Jennifer L Mazzola, Michael A Sirover
Sep 10, 2002·Human Molecular Genetics·Hiroko KitaKikuya Kato
Apr 8, 2004·Molecular Cell·Ronald A Butow, Narayan G Avadhani
Apr 28, 2004·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·J Lawrence Marsh, Leslie Michels Thompson
Jun 22, 2005·Molecular & Cellular Proteomics : MCP·Marzia PerluigiD Allan Butterfield
Nov 16, 2005·Annual Review of Genetics·Julide Bilen, Nancy M Bonini
Nov 18, 2005·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Sung-Jin JeongYoo-Hun Suh
Feb 3, 2006·Molecular Biology of the Cell·Alexandra BenchouaEmmanuel Brouillet
Feb 13, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Joshua R DusickNeil A Martin
Feb 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·William J PowersJoel S Perlmutter
Feb 17, 2007·Neuroscience·E Trushina, C T McMurray
Aug 30, 2007·Proceedings of the National Academy of Sciences of the United States of America·Hemant VarmaBrent R Stockwell
Sep 19, 2007·Neurobiology of Aging·Tiziana CoccoGaetano Villani
Sep 26, 2007·Brain : a Journal of Neurology·A FeiginD Eidelberg
Oct 3, 2007·Cell Metabolism·Keith D Baker, Carl S Thummel
Jun 26, 2008·American Journal of Physiology. Endocrinology and Metabolism·Ian A SimpsonSusan J Vannucci
Jul 1, 2008·The European Journal of Neuroscience·Joana M Gil, Ana Cristina Rego
Jul 1, 2008·Free Radical Biology & Medicine·Ma Alba SorollaElisa Cabiscol
Sep 24, 2008·The Journal of Biological Chemistry·Susan K LeganWilliam C Orr
Oct 17, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Caroline L BennJang-Ho J Cha
Dec 17, 2008·Annals of the New York Academy of Sciences·Edward C StackRobert J Ferrante
Dec 17, 2008·Annals of the New York Academy of Sciences·Susan E Browne
Dec 17, 2008·Annals of the New York Academy of Sciences·Rajnish K Chaturvedi, M Flint Beal

❮ Previous
Next ❯

Citations

Aug 5, 2015·Journal of Neuroscience Methods·Elizabeth A Lewis, Gaynor A Smith
Nov 11, 2017·Journal of Huntington's Disease·Janet M Dubinsky
Feb 28, 2019·Aging Cell·Lifen WangHeinrich Jasper
Jun 11, 2019·ELife·Ernesto ManzoDaniela C Zarnescu
Apr 26, 2017·The EMBO Journal·Simonetta Camandola, Mark P Mattson
Apr 3, 2020·Journal of Cellular Physiology·Bor Luen Tang
May 28, 2019·Journal of Cellular Biochemistry·Bor Luen Tang
Nov 20, 2016·Journal of Alzheimer's Disease : JAD·Leszek Szablewski
Jun 2, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·Jing LiXinsheng Lai
Jan 12, 2021·Biochemical and Biophysical Research Communications·Kinga GłuchowskaLeszek Szablewski
Oct 15, 2020·International Journal of Molecular Sciences·Francesca Di CristoGianfranco Peluso
Aug 15, 2021·Trends in Pharmacological Sciences·Adriana A GarciaDaria Mochly-Rosen
Aug 24, 2021·Metabolism: Clinical and Experimental·Wuxue PengLifen Chen
Apr 14, 2021·CNS & Neurological Disorders Drug Targets·Iqra Subhan, Yasir Hasan Siddique

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
FRET
PCR
transfection

Software Mentioned

AmplifX
GraphPad Prism
Excel
Image J

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.