{"id":15949,"date":"2018-01-08T00:00:19","date_gmt":"2018-01-08T08:00:19","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=15949"},"modified":"2018-01-09T08:52:14","modified_gmt":"2018-01-09T16:52:14","slug":"alzheimers-drug-turns-back-clock-powerhouse-cell","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/de\/news-release\/alzheimers-drug-turns-back-clock-powerhouse-cell\/","title":{"rendered":"Alzheimer\u2019s drug turns back clock in powerhouse of cell"},"content":{"rendered":"

LA JOLLA\u2014The experimental drug J147 is something of a modern elixir of life; it\u2019s been shown to treat Alzheimer\u2019s disease and reverse aging in mice and is almost ready for clinical trials in humans. Now, Salk scientists have solved the puzzle of what, exactly, J147 does. In a paper published January 7, 2018, in the journal Aging Cell<\/em><\/a>, they report that the drug binds to a protein found in mitochondria, the energy-generating powerhouses of cells. In turn, they showed, it makes aging cells, mice and flies appear more youthful.<\/p>\n

\"\"
Caption: A pipette of J147 from the Schubert lab. Credit: Salk Institute<\/figcaption><\/figure>\n

\u201cThis really glues together everything we know about J147 in terms of the link between aging and Alzheimer\u2019s,\u201d says Dave Schubert<\/a>, head of Salk\u2019s Cellular Neurobiology Laboratory and the senior author on the new paper. \u201cFinding the target of J147 was also absolutely critical in terms of moving forward with clinical trials.\u201d<\/p>\n

Schubert\u2019s group developed J147 in 2011, after screening for compounds from plants with an ability to reverse the cellular and molecular signs of aging in the brain. J147 is a modified version of a molecule (curcumin) found in the curry spice turmeric. In the years since, the researchers have shown that the compound reverses memory deficits, potentiates the production of new brain cells, and slows or reverses Alzheimer\u2019s progression in mice<\/a>. However, they didn\u2019t know how J147 worked at the molecular level.<\/p>\n

In the new work, led by Schubert and Salk Research Associate Josh Goldberg, the team used several approaches to home in on what J147 is doing. They identified the molecular target of J147 as a mitochondrial protein called ATP synthase that helps generate ATP\u2014the cell\u2019s energy currency\u2014within mitochondria. They showed that by manipulating its activity, they could protect neuronal cells from multiple toxicities associated with the aging brain. Moreover, ATP synthase has already been shown to control aging in C. elegans <\/em>worms and flies.<\/p>\n

\u201cWe know that age is the single greatest contributing factor to Alzheimer\u2019s, so it is not surprising that we found a drug target that\u2019s also been implicated in aging,\u201d says Goldberg, the paper’s first author.<\/p>\n

Further experiments revealed that modulating activity of ATP synthase with J147 changes the levels of a number of other molecules\u2014including levels of ATP itself\u2014and leads to healthier, more stable mitochondria throughout aging and in disease.<\/p>\n

\u201cI was very surprised when we started doing experiments with how big of an effect we saw,\u201d says Schubert. \u201cWe can give this to old mice and it really elicits profound changes to make these mice look younger at a cellular and molecular level.\u201d<\/p>\n

The results, the researchers say, are not only encouraging for moving the drug forward as an Alzheimer\u2019s treatment, but also suggest that J147 may be useful in other age-associated diseases as well.<\/p>\n

\u201cPeople have always thought that you need separate drugs for Alzheimer\u2019s, Parkinson\u2019s and stroke\u201d says Schubert. \u201cBut it may be that by targeting aging we can treat or slow down many pathological conditions that are old-age-associated.\u201d<\/p>\n

The team is already performing additional studies on the molecules that are altered by J147\u2019s effect on the mitochondrial ATP synthase\u2014which could themselves be new drug targets. J147 has completed the FDA-required toxicology testing in animals, and funds are being sought to initiate phase 1 clinical trials in humans.<\/p>\n

Other researchers on the study were A. Currais, M. Prior, W. Fischer, C. Chiruta, D. Daugherty, R. Dargusch and P. Maher of the Salk Institute; E. Ratliff and K. Finley of San Diego State University; P.B. Esparza-Molto and J.M. Cuezva of the Universidad Autonoma de Madrid; and M. Petrascheck of The Scripps Research Institute.<\/p>\n

The work and the researchers involved were supported by grants from the National Institutes of Health, California Institute of Regenerative Medicine, the Nomis Foundation, the Della Thome Foundation, the Bundy Foundation, the Hewitt Foundation, the Paul F. Glenn Center for Aging Research at the Salk Institute and the Waitt Foundation.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[113],"disease-research":[127,146],"class_list":["post-15949","disclosure","type-disclosure","status-publish","hentry","faculty-dave-schubert","disease-research-alzheimers-disease","disease-research-aging-and-regenerative-medicine"],"acf":[],"yoast_head":"\nAlzheimer\u2019s drug turns back clock in powerhouse of cell - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/de\/news-release\/alzheimers-drug-turns-back-clock-powerhouse-cell\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Alzheimer\u2019s drug turns back clock in powerhouse of cell - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014The experimental drug J147 is something of a modern elixir of life; it\u2019s been shown to treat Alzheimer\u2019s disease and reverse aging in mice and is almost ready for clinical trials in humans. 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