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Rapamycin gets its name from Rapa Nui, the native term for Easter Island. In the 1960s, scientists went to the island in search of new antimicrobials. They found that the island’s soil harbors bacteria that contain “a compound with remarkable antifungal, immunosuppressive, and antitumor properties.”
For many years, scientists have believed that rapamycin exerts most of its effect by blocking the appropriately-named mechanistic target of rapamycin (mTOR). However, they also suspected that the drug might work through more than just this cell signaling pathway. Now, by uncovering a second cell target for rapamycin, a recent study offers valuable insights into the drug’s potential as a neuroprotective, anti-ageing agent.
Accumulation of faulty proteins in cells is a characteristic of aging. It is also a hallmark of Alzheimer’s, Parkinson’s, and other neurodegenerative diseases. The study is the work of researchers at the University of Michigan in Ann Arbor and the Zhejiang University of Technology in China. They report their findings in a recent PLOS Biology paper.
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The principal study investigator is Haoxing Xu, who supervises a laboratory in the Department of Molecular, Cellular, and Developmental Biology, at the University of Michigan.
“The identification of a new target of rapamycin offers an insight in developing the next generation of rapamycin, which will have a more specific effect on neurodegenerative disease,” says co-lead study author Wei Chen, who works in Xu’s laboratory.
Rapamycin and autophagy
Since the discovery of rapamycin, its various uses as an immune suppressor have extended from preventing immune rejection of organ transplants to the coating of stents that prop open coronary arteries. Autophagy is the process of cellular self-destruction and occurs in every human to recycle old cells.
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The Food and Drug Administration (FDA) have also approved several rapamycin derivatives, or “rapalogs,” for clinical trials to evaluate their effectiveness in targeting cancer cells and treating neurodegenerative diseases. In addition, studies in mammals, flies, and other organisms have shown that rapamycin can lengthen lifespan.
When rapamycin blocks mTOR, it halts cell growth. However, blocking mTOR also sets autophagy in motion. Autophagy is another cell process that clears away and recycles damaged cell components and proteins that have the wrong shape and do not work correctly. That is why drug developers are interested in its potential as an anticancer agent because uncontrolled growth of cells is a primary feature of cancer.