title: The small molecule AUTEN-99 (autophagy enhancer-99) prevents the progression of neurodegenerative symptoms.
abstract: Autophagy functions as a main route for the degradation of superfluous and damaged constituents of the cytoplasm. Defects in autophagy are implicated in the development of various age-dependent degenerative disorders such as cancer, neurodegeneration and tissue atrophy, and in accelerated aging. To promote basal levels of the process in pathological settings, we previously screened a small molecule library for novel autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negative regulator of autophagic membrane formation. Here we identify AUTEN-99 (autophagy enhancer-99), which activates autophagy in cell cultures and animal models. AUTEN-99 appears to effectively penetrate through the blood-brain barrier, and impedes the progression of neurodegenerative symptoms in Drosophila models of Parkinson's and Huntington's diseases. Furthermore, the molecule increases the survival of isolated neurons under normal and oxidative stress-induced conditions. Thus, AUTEN-99 serves as a potent neuroprotective drug candidate for preventing and treating diverse neurodegenerative pathologies, and may promote healthy aging.
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, H-6726, Hungary.|Department of Genetics, Eötvös Loránd University, Budapest, H-1117, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Kovács
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, H-6726, Hungary.
authors.forename: Viktor
authors.initials: V
authors.lastname: Billes
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, H-6726, Hungary.
authors.forename: Marcell
authors.initials: M
authors.lastname: Komlós
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, H-6726, Hungary.|Department of Genetics, Eötvös Loránd University, Budapest, H-1117, Hungary.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Hotzi
authors.affiliation: Department of Genetics, Eötvös Loránd University, Budapest, H-1117, Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Manzéger
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, H-6726, Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Tarnóci
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, H-6726, Hungary.
authors.forename: Diána
authors.initials: D
authors.lastname: Papp
authors.affiliation: Department of Genetics, Eötvös Loránd University, Budapest, H-1117, Hungary.
authors.forename: Fanni
authors.initials: F
authors.lastname: Szikszai
authors.affiliation: Department of Genetics, Eötvös Loránd University, Budapest, H-1117, Hungary.
authors.forename: Janka
authors.initials: J
authors.lastname: Szinyákovics
authors.affiliation: Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, H-1092, Hungary.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Rácz
authors.affiliation: Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, H-1092, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Noszál
authors.affiliation: Group of Biological Barriers, Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, H-6726, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Veszelka
authors.affiliation: Group of Biological Barriers, Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, H-6726, Hungary.
authors.forename: Fruzsina R
authors.initials: FR
authors.lastname: Walter
authors.affiliation: Group of Biological Barriers, Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, H-6726, Hungary.
authors.forename: Mária A
authors.initials: MA
authors.lastname: Deli
authors.affiliation: Avidin Ltd., Szeged, H-6726, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Hackler
authors.affiliation: Avidin Ltd., Szeged, H-6726, Hungary.
authors.forename: Robert
authors.initials: R
authors.lastname: Alfoldi
authors.affiliation: Avidin Ltd., Szeged, H-6726, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Huzian
authors.affiliation: Avidin Ltd., Szeged, H-6726, Hungary.
authors.forename: Laszlo G
authors.initials: LG
authors.lastname: Puskas
authors.affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, H-1117, Hungary.
authors.forename: Hanna
authors.initials: H
authors.lastname: Liliom
authors.affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, H-1117, Hungary.
authors.forename: Krisztián
authors.initials: K
authors.lastname: Tárnok
authors.affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, H-1117, Hungary.|MTA-ELTE NAP B Neuronal Cell Biology Research Group, Eötvös Loránd University, Budapest, H-1117, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Schlett
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Budapest, H-1117, Hungary.
authors.forename: Adrienn
authors.initials: A
authors.lastname: Borsy
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Budapest, H-1117, Hungary.
authors.forename: Ervin
authors.initials: E
authors.lastname: Welker
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, H-1117, Hungary.
authors.forename: Attila L
authors.initials: AL
authors.lastname: Kovács
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, H-6726, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Pádár
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, H-6726, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Erdős
authors.affiliation: Department of Cell Biology and Molecular Medicine, University of Szeged, Szeged, H-6720, Hungary.
authors.forename: Adam
authors.initials: A
authors.lastname: Legradi
authors.affiliation: Department of Cell Biology and Molecular Medicine, University of Szeged, Szeged, H-6720, Hungary.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Bjelik
authors.affiliation: Department of Cell Biology and Molecular Medicine, University of Szeged, Szeged, H-6720, Hungary.
authors.forename: Károly
authors.initials: K
authors.lastname: Gulya
authors.affiliation: Karolinska Institute, Department of Clinical Neuroscience, S-171 76 Stockholm, Sweden.|Lee Kong Chian School of Medicine, Nanyang Technological University, 636921 Singapore.|Imperial College London, Department of Medicine, Division of Brain Sciences, London, SW7 2AZ, UK.
authors.forename: Balázs
authors.initials: B
authors.lastname: Gulyás
authors.affiliation: Velgene Biotechnology Research Ltd., Szeged, H-6726, Hungary.|Department of Genetics, Eötvös Loránd University, Budapest, H-1117, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Vellai
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004330:Drosophila; D019636:Neurodegenerative Diseases / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D018696:Neuroprotective Agents