title: AUTEN-67 (Autophagy Enhancer-67) Hampers the Progression of Neurodegenerative Symptoms in a Drosophila model of Huntington's Disease.
abstract: Autophagy, a lysosome-mediated self-degradation process of eukaryotic cells, serves as a main route for the elimination of cellular damage [1-3]. Such damages include aggregated, oxidized or misfolded proteins whose accumulation can cause various neurodegenerative pathologies, including Huntington's disease (HD).
  
  
  
  Here we examined whether enhanced autophagic activity can alleviate neurophatological features in a Drosophila model of HD (the transgenic animals express a human mutant Huntingtin protein with a long polyglutamine repeat, 128Q).
  
  
  
  We have recently identified an autophagy-enhancing small molecule, AUTEN-67 (autophagy enhancer 67), with potent neuroprotective effects [4]. AUTEN-67 was applied to induce autophagic activity in the HD model used in this study.
  
  
  
  We showed that AUTEN-67 treatment interferes with the progressive accumulation of ubiquitinated proteins in the brain of Drosophila transgenic for the pathological 128Q form of human Huntingtin protein. The compound significantly improved the climbing ability and moderately extended the mean life span of these flies. Furthermore, brain tissue samples from human patients diagnosed for HD displayed increased levels of the autophagy substrate SQSTM1/p62 protein, as compared with controls.
  
  
  
  These results imply that AUTEN-67 impedes the progression of neurodegenerative symptoms characterizing HD, and that autophagy is a promising therapeutic target for treating this pathology. In humans, AUTEN-67 may have the potential to delay the onset and decrease the severity of HD.
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, Hungary.
authors.forename: Viktor
authors.initials: V
authors.lastname: Billes
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, Hungary.|Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Kovács
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, Hungary.|Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Hotzi
authors.affiliation: Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Manzéger
authors.affiliation: Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Kinga
authors.initials: K
authors.lastname: Tagscherer
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, Hungary.
authors.forename: Marcell
authors.initials: M
authors.lastname: Komlós
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Tarnóci
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Pádár
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Erdős
authors.affiliation: Department of Cell Biology and Molecular Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Bjelik
authors.affiliation: Department of Cell Biology and Molecular Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Adam
authors.initials: A
authors.lastname: Legradi
authors.affiliation: Department of Cell Biology and Molecular Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Károly
authors.initials: K
authors.lastname: Gulya
authors.affiliation: Karolinska Institute, Department of Clinical Neuroscience, Stockholm, Sweden.|Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.|Imperial College London, Department of Medicine, Division of Brain Sciences, London, UK.
authors.forename: Balázs
authors.initials: B
authors.lastname: Gulyás
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, Hungary.|Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Vellai
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001343:Autophagy / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics; D006816:Huntington Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology; D009285:Naphthoquinones / Q000378:metabolism / Q000627:therapeutic use*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000235:genetics; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010455:Peptides / Q000235:genetics; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000378:metabolism / Q000627:therapeutic use*; D000096926:Benzenesulfonamides
chemical_list: D029721:Drosophila Proteins; D000071058:Huntingtin Protein; D009285:Naphthoquinones; D018696:Neuroprotective Agents; D010455:Peptides; D013449:Sulfonamides; C086055:HTT protein, human; C000612165:N-(3-(benzimidazol-1-yl)-1,4-dioxonaphthalen-2-yl)-4-nitrobenzenesulfonamide; D000096926:Benzenesulfonamides; C097188:polyglutamine
keywords: AUTEN-67; Drosophila; Huntingtin; Huntington’s disease; Ref(2)P/SQSTM1/p62; autophagy; climbing assay; neurodegeneration; polyQ; ubiquitinated proteins