Japanese scientists have made further advances in understanding the cellular process of autophagy, its effects on degenerative diseases such as Alzheimer's and Parkinson's, and finding medicines that can treat them.
The researchers developed a simple method for quantitatively measuring autophagic activity, the cellular “self-devouring” process in which a cell degrades part of its protein to recycle nutrients.
The study was featured in the online edition of the U.S. journal Molecular Cell on Nov. 5. Its publication came soon after Yoshinori Ohsumi, an honorary professor at the Tokyo Institute of Technology, won the 2016 Nobel Prize in Physiology or Medicine for his discoveries of mechanisms of autophagy.
The researchers, including Noboru Mizushima, a professor in the Department of Biochemistry and Molecular Biology at the University of Tokyo’s Graduate School of Medicine, developed a method to easily monitor and measure autophagic flux.
Measuring autophagic activity is of great significance, but complicated and challenging. Not only is the autophagic process thought to occur in neurodegenerative diseases including Alzheimer's and Parkinson's, it is also believed to be related to the onset of various diseases such as cancers and infections.
The results of the study are to be used in other studies to examine the effects of autophagic activity on diseases as well as the search for medicines that modulate autophagy.
The team devised the method for measuring autophagic activity by comparing the ratio of protein between samples that are degrading and others that are not, suggesting autophagy-modulating effects.
With this new method, autophagy induction was monitored not only in cultured cells but also in zebrafish eyes and the fertilized eggs of mice.
To search for autophagy-modulating medicines, the team also examined how 1,054 approved drugs, including antimicrobial agents and anticancer drugs, affect autophagic activity, screening the drugs to identify autophagy inducers and inhibitors with the new method.
They found that 47 drugs induced autophagic processes, while 43 drugs inhibited them.
Thirteen drugs previously reported as either autophagy inducers or inhibitors actually showed the opposite modulations in the study.
http://www.asahi.com/ajw/articles/AJ201611230001.html
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