AUTEN-67 (Autophagy Enhancer-67) Hampers the Progression of Neurodegenerative Symptoms in a Drosophila model of Huntington's Disease

Journal of Huntington's Disease

Volumn 5, Issue 2, 2016, Pages 133-147

  Billesa, Viktor ^a   Kovacs, Tibor ^a,b   Hotzi, Bernadette ^a,b   Manzeger, Anna ^b   Tagscherer, Kinga ^b   Komlos, Marcell ^a   Tarnocia, Anna ^a   Padar, Zsolt ^a   Erdos, Attila ^c   Bjelik, Annamaria ^c   Legradi, Adam ^c   Gulya, Karoly ^c   Gulyas, Balazs ^d,e,f   Vellai, Tibor ^a,b  

^a Velgene Biotechnology Research Ltd   (Hungary)

^b EÖTVÖS LORÁND UNIVERSITY   (Hungary)

^c UNIVERSITY OF SZEGED   (Hungary)

^d KAROLINSKA INSTITUTE   (Sweden)

^e NANYANG TECHNOLOGICAL UNIVERSITY   (Singapore)

^f IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

autophagy, AUTEN 67; climbing assay; Drosophila; Huntingtin; Huntington's disease; neurodegeneration; polyq; Ref(2)P SQSTM1 p62; ubiquitinated proteins

Indexed keywords

AUTOPHAGY ENHANCER 67; HUNTINGTIN; MUTANT PROTEIN; NEUROPROTECTIVE AGENT; POLYGLUTAMINE; PROTEIN P62; SEQUESTOSOME 1 PROTEIN; UBIQUITINATED PROTEIN; UNCLASSIFIED DRUG; DROSOPHILA PROTEIN; HTT PROTEIN, HUMAN; N-(3-(BENZIMIDAZOL-1-YL)-1,4-DIOXONAPHTHALEN-2-YL)-4-NITROBENZENESULFONAMIDE; NAPHTHOQUINONE; PEPTIDE; SULFONAMIDE;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AUTOPHAGY; BRAIN TISSUE; CLIMBING; CONTROLLED STUDY; DEGENERATIVE DISEASE; DISEASE COURSE; DRUG MECHANISM; FEMALE; FRUIT FLY MODEL; HUMAN; HUMAN TISSUE; HUNTINGTON CHOREA; LIFE EXTENSION; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN CONTENT; TISSUE LEVEL; TRANSGENIC DROSOPHILA; TREATMENT OUTCOME; ANIMAL; BRAIN; COMPLICATION; DISEASE MODEL; DROSOPHILA; DRUG EFFECTS; GENETICS; METABOLISM; NEURODEGENERATIVE DISEASES; NONPARAMETRIC TEST; PATHOLOGY; TRANSGENIC ANIMAL;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; AUTOPHAGY; BRAIN; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; DROSOPHILA; DROSOPHILA PROTEINS; HUMANS; HUNTINGTIN PROTEIN; HUNTINGTON DISEASE; NAPHTHOQUINONES; NEURODEGENERATIVE DISEASES; NEUROPROTECTIVE AGENTS; PEPTIDES; STATISTICS, NONPARAMETRIC; SULFONAMIDES;

EID: 84991387218     PISSN: 18796397     EISSN: 18796400     Source Type: Journal    
DOI: 10.3233/JHD-150180     Document Type: Article

References (42)

1. Klionsky DJ. The molecular machinery of autophagy: Unanswered questions. J Cell Sci. 2005;118(Pt 1):7-18.
2. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008;451(7182):1069-75.
3. Vellai T, Takacs-Vellai K, Sass M, Klionsky DJ. The regulation of aging: Does autophagy underlie longevity Trends Cell Biol. 2009;19(10):487-94.
4. Papp D, Kovacs T, Billes V, Varga M, Tarnoci A, Hackler L, et al. AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects. Autophagy. 2015;12(2):273-86.
5. Walker FO. Huntington's disease. Lancet. 2007;369(9557):218-28.
6. Sarkar S, Rubinsztein DC. Huntington's disease: Degradation of mutant huntingtin by autophagy. FEBS J. 2008;275(17):4263-70.
7. Bjørkøy G, Lamark T, Brech A, Outzen H, Perander M, et al. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol. 2005;171(4):603-14.
8. Filimonenko M, Isakson P, Finley KD, Anderson M, Jeong H, et al. The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy. Mol Cell. 2010;38(2):265-79.
9. Lu K, Psakhye I, Jentsch S. Autophagic clearance of polyQ proteins mediated by ubiquitin-Atg8 adaptors of the conserved CUET protein family. Cell. 2014;158(3):549-63.
10. Del Toro D, Alberch J, Lazaro-Dieguez F, Martin-Ibanez R, Xifro X, et al. Mutant huntingtin impairs post-Golgi trafficking to lysosomes by delocalizing optineurin/Rab8 complex from the Golgi apparatus. Mol Biol Cell. 2009;20(5):1478-92.
11. Martinez-Vicente M, Talloczy Z, Wong E, Tang G, Koga H, et al. Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease. Nat Neurosci. 2010;13(5):567-76.
12. Wong YC, Holzbaur EL. The regulation of autophagosome dynamics by huntingtin and HAP1 is disrupted by expression of mutant huntingtin, leading to defective cargo degradation. J Neurosci. 2014;34(4):1293-305.
13. Martin DD, Ladha S, Ehrnhoefer DE, Hayden MR. Autophagy in Huntington disease and huntingtin in autophagy. Trends Neurosci. 2015;38(1):26-35.
14. Ochaba J, Lukacsovich T, Csikos G, Zheng S, Margulis J, et al. Potential function for the Huntingtin protein as a scaffold for selective autophagy. Proc Natl Acad Sci USA. 2014;111(47):16889-94.
15. Rui YN, Xu Z, Patel B, Chen Z, Chen D, et al. Huntingtin functions as a scaffold for selective macroautophagy. Nat Cell Biol. 2015;17(3):262-75.
16. Yu X, Long YC, Shen HM. Differential regulatory functions of three classes of phosphatidylinositol and phosphoinositide 3-kinases in autophagy. Autophagy. 2015;11(10):1711-28.
17. Robinson FL, Dixon JE. Myotubularin phosphatases: Policing 3-phosphoinositides. Trends Cell Biol. 2006;16(8):403-12.
18. Vergne I, Roberts E, Elmaoued RA, Tosch V, Delgado MA, Proikas-Cezanne T, et al. Control of autophagy initiation by phosphoinositide 3-phosphatase Jumpy. EMBO J. 2009;28(15):2244-58.
19. Takacs-Vellai K, Bayci A, Vellai T. Autophagy in neuronal cell loss: A road to death. Bioessays. 2006;28(11):1126-31.
20. Yuan J, Kroemer G. Alternative cell death mechanisms in development and beyond. Genes Dev. 2010;24(23):2592-602.
21. Vellai T. Autophagy genes and ageing. Cell Death Differ. 2009;16(1):94-102.
22. Toth ML, Sigmond T, Borsos E, Barna J, Erdelyi P, Takacs-Vellai K, et al. Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy. 2008;4(3):330-8.
23. Lopez-Otn C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-217.
24. Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132(1):27-42.
25. Rubinsztein DC. The roles of intracellular proteindegradation pathways in neurodegeneration. Nature. 2006;443(7113):780-6.
26. Sarkar S, Perlstein EO, Imarisio S, Pineau S, Cordenier A, Maglathlin RL, et al. Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. Nat Chem Biol. 2007;3(6):331-8.
27. Fleming A, Noda T, Yoshimori T, Rubinsztein DC. Chemical modulators of autophagy as biological probes and potential therapeutics. Nat Chem Biol. 2011;7(1):9-17.
28. Chang YY, Neufeld TP. An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation. Mol Biol Cell. 2009;20(7):2004-14.
29. Pircs K, Nagy P,VargaA,Venkei Z, Erdi B, et al. Advantages and limitations of different p62-based assays for estimating autophagic activity in Drosophila. PloS One. 2012; 7:e44214.
30. Szigeti C, Bencsik N, Simonka JA, Legradi A, Kasa P, Gulya K. Long-term effects of selective immunolesions of cholinergic neurons of the nucleus basalis magnocellularis\ on the ascending cholinergic pathways in the rat: A model for Alzheimer's disease. Brain Res Bull. 2013;94:9-16.
31. Szabo M, Gulya K. Development of the microglial phenotype in culture. Neuroscience. 2013;241:280-95.
32. Abràmoff MD, Magalhães PJ, Ram SJ. Image processing with ImageJ. Biophotonics Int. 2004;11(7):36-42.
33. Romero E, Cha GH, Verstreken P, Ly CV, Hughes RE, Bellen HJ, et al. Suppression of neurodegeneration and increased neurotransmission caused by expanded fulllength huntingtin accumulating in the cytoplasm. Neuron. 2008;57(1):27-40.
34. Gonzales E, Yin J. Drosophila models of Huntington's disease exhibit sleep abnormalities. PLoS Curr. 2010;2.
35. Mauvezin C, Ayala C, Braden CR, Kim J, Neufeld TP. Assays to monitor autophagy in Drosophila. Methods. 2014;68(1):134-9.
36. Avila A, Silverman N, Diaz-Meco MT, Moscat J. The Drosophila atypical protein kinase C-Ref(2)P complex constitutes a conserved module for signaling in the toll pathway. Mol Cell Biol. 2002;22(24):8787-95.
37. Nezis IP, Simonsen A, Sagona AP, Finley K, Gaumer S, Contamine D, et al. Ref(2)P, the Drosophila melanogaster homologue of mammalian p62, is required for the formation of protein aggregates in adult brain. J Cell Biol. 2008;180(6):1065-71.
38. Nagaoka U, Kim K, Jana NR, Doi H, Maruyama M, et al. Increased expression of p62 in expanded polyglutamineexpressing cells and its association with polyglutamine inclusions. J Neurochem. 2004; 91(1):57-68.
39. Goldberg AL. Protein degradation and protection against misfolded or damaged proteins. Nature. 2003;426(6968):895-9.
40. Sieradzan KA, Mechan AO, Jones L, Wanker EE, Nukina N, Mann DM. Huntington's disease intranuclear inclusions contain truncated, ubiquitinated huntingtin protein. Exp Neurol. 1999;156(1):92-9.
41. Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S, et al. Inhibition ofmTORinduces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet. 2004;36(6):585-95.
42. Hnia K, Vaccari I, Bolino A, Laporte J. Myotubularin phosphoinositide phosphatases: Cellular functions and disease pathophysiology. Trends Mol Med. 2012;18(6):317-27.