2. Academic Validation
  3. The small molecule AUTEN-99 (autophagy enhancer-99) prevents the progression of neurodegenerative symptoms

The small molecule AUTEN-99 (autophagy enhancer-99) prevents the progression of neurodegenerative symptoms

  • Sci Rep. 2017 Feb 16;7:42014. doi: 10.1038/srep42014.
Tibor Kovács 1 2,  Viktor Billes 1,  Marcell Komlós 1,  Bernadette Hotzi 1 2,  Anna Manzéger 2,  Anna Tarnóci 1,  Diána Papp 1,  Fanni Szikszai 2,  Janka Szinyákovics 2,  Ákos Rácz 3,  Béla Noszál 3,  Szilvia Veszelka 4,  Fruzsina R Walter 4,  Mária A Deli 4,  Laszlo Hackler Jr 5,  Robert Alfoldi 5,  Orsolya Huzian 5,  Laszlo G Puskas 5,  Hanna Liliom 6,  Krisztián Tárnok 6,  Katalin Schlett 6 7,  Adrienn Borsy 8,  Ervin Welker 8,  Attila L Kovács 9,  Zsolt Pádár 1,  Attila Erdős 1,  Adam Legradi 10,  Annamaria Bjelik 10,  Károly Gulya 10,  Balázs Gulyás 11 12 13,  Tibor Vellai 1 2
Affiliations

Affiliations

  • 1 Velgene Biotechnology Research Ltd., Szeged, H-6726, Hungary.
  • 2 Department of Genetics, Eötvös Loránd University, Budapest, H-1117, Hungary.
  • 3 Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, H-1092, Hungary.
  • 4 Group of Biological Barriers, Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, H-6726, Hungary.
  • 5 Avidin Ltd., Szeged, H-6726, Hungary.
  • 6 Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, H-1117, Hungary.
  • 7 MTA-ELTE NAP B Neuronal Cell Biology Research Group, Eötvös Loránd University, Budapest, H-1117, Hungary.
  • 8 Institute of Enzymology, Research Centre for Natural Sciences, Budapest, H-1117, Hungary.
  • 9 Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, H-1117, Hungary.
  • 10 Department of Cell Biology and Molecular Medicine, University of Szeged, Szeged, H-6720, Hungary.
  • 11 Karolinska Institute, Department of Clinical Neuroscience, S-171 76 Stockholm, Sweden.
  • 12 Lee Kong Chian School of Medicine, Nanyang Technological University, 636921 Singapore.
  • 13 Imperial College London, Department of Medicine, Division of Brain Sciences, London, SW7 2AZ, UK.
PMID: 28205624 DOI: 10.1038/srep42014
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.

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