Identification of a Potential Autophagy Enhancement Drug

Researchers here note the identification of a drug candidate to enhance autophagy, a process of cellular housekeeping responsible for removing damaged proteins and structures in the cell. Enhanced autophagy is associated with many of the interventions known to slow aging in laboratory species, and in at least some cases, such as for calorie restriction, the correct operation of autophagy has been shown to be necessary for extension of life span to take place. Consequently, the research community has for some time shown interest in the development of therapies based on the enhancement of autophagy, but there has been surprisingly little progress on this front to date.

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.

Link: https://dx.doi.org/10.1038/srep42014

Comments

This looks promising, but then I am an autophagy fan boy. The life span extention in mice was only about 7% though. This may be dose dependent, but I could not find any discussion on the doses given to the mice or disscussion on possible additive or synergistic effects with other inducers of autophagy. It actually seems like a lot of info was intentionally withheld from the publication.

Posted by: JohnD at February 21st, 2017 11:25 AM

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