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AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects.

Papp, Diána and Kovács, Tibor and Billes, Viktor András and Varga, Máté and Tarnóci, Anna and Puskás, László and Liliom, Hanna Laura and Tárnok, Krisztián and Schlett, Katalin and Borsy, Adrienn Éva and Pádár, Zsolt and Kovács, Attila Lajos and Hegedűs, Krisztina and Juhász, Gábor and Vellai, Tibor and Hackler Jr., László and Komlós, Marcell and Erdős, Attila and Gulyás, Balázs (2016) AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects. AUTOPHAGY, 12 (2). pp. 273-286. ISSN 1554-8627

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Abstract

Autophagy is a major molecular mechanism that eliminates cellular damage in eukaryotic organisms. Basal levels of autophagy are required for maintaining cellular homeostasis and functioning. Defects in the autophagic process are implicated in the development of various age-dependent pathologies including cancer and neurodegenerative diseases, as well as in accelerated aging. Genetic activation of autophagy has been shown to retard the accumulation of damaged cytoplasmic constituents, delay the incidence of age-dependent diseases and extend life span in genetic models. This implies that autophagy serves as a therapeutic target in treating such pathologies. Although several autophagy-inducing chemical agents have been identified, the majority of them operate upstream of the core autophagic process, thereby exerting undesired side effects. Here, we screened a small-molecule library for specific inhibitors of MTMR14, a myotubularin-related phosphatase antagonizing the formation of autophagic membrane structures, and isolated AUTEN-67 (autophagy enhancer-67) that significantly increases autophagic flux in cell lines and in vivo models. AUTEN-67 promotes longevity and protects neurons from undergoing stress-induced cell death. It also restores nesting behavior in a murine model of Alzheimer disease, without apparent side effects. Thus, AUTEN-67 is a potent drug candidate for treating autophagy-related diseases.

Item Type: Article
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 09 Feb 2017 14:04
Last Modified: 09 Feb 2017 14:04
URI: http://real.mtak.hu/id/eprint/48012

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