An antibiotic could protect against age-related brain diseases



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An antibiotic, minocycline, can increase the lifespan of roundworms by preventing protein accumulation during aging, study published in the journal for free access eLife reports.

The aggregation of proteins is at the origin of several age-related progressive brain diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease and prion disease. . This study shows that minocycline prevents this accumulation even in older animals whose stress response pathways are altered by age.

The number of proteins in a cell is balanced by the rate of manufacture and elimination of proteins, called proteostasis. As you get older, the proteostasis becomes impaired. "It would be great if there was a way to improve proteostasis and prolong life span and health, by treating the elderly at the first sign of neurodegenerative symptoms or markers of disease such as diabetes." Protein accumulation, "says lead author Gregory Solis, a graduate student at Scripps Research, US. "In this study, we investigated whether minocycline could reduce protein aggregation and prolong the lifespan of animals already showing impaired proteostasis."

The team first tested 21 different molecules known to extend the life of both young and old patients. Caenorhabditis elegans (C. elegans) towards. They found that all these molecules prolonged the lives of young worms; However, the only drug effective against older worms was minocycline.

To find out why, they examined whether minocycline had an effect on protein aggregation in worms. They treated the young and old worms with water or minocycline and then measured two proteins called α-synuclein and amyloid-β, known to develop in Parkinson's and Alzheimer's diseases, respectively. Regardless of the age of worms, those who were treated with minocycline exhibited reduced aggregation of both proteins as they grew up without even activating stress responses.

The team then became interested in the mechanism at the origin of this discovery. First, they sought to know if minocycline activated the altered stress signaling proteins in older worms, but they found that the drug actually reduced their activity. Then they studied whether it disabled the process of removing protein from the cell, but that was not its mode of action either.

When they used a chemical probe to see how minocycline affects the major protein regulatory molecules in the cell, they revealed that minocycline directly affects the cell's protein-making mechanism called the ribosome. This was true for worms, as well as for mouse and human cells.

Finally, the team used worms with increased or decreasing protein production activity and studied the effect of this alteration on the effect of minocycline on protein levels and shelf life. As expected, in mutant worms where protein production had already decreased, they found that a lower dose of minocycline was needed to further reduce protein levels and prolong life. In worms where protein production has increased, the reverse has been observed. This suggests that minocycline prolongs the shelf life by controlling the rate of ribosome protein production.

"We have identified minocycline as a drug that can extend the shelf life and improve the protein balance in already aging worms," ​​concludes Michael Petrascheck, PhD, lead author of the article and associate professor at Scripps. Research. "Our study reveals how minocycline prevents protein aggregation and lays the foundation for drug development efforts to optimize this already approved drug for a wide range of neurodegenerative diseases."

Source:

https://elifesciences.org/for-the-press/57d6122a/antibiotic-could-protect-against-neurode-energenerative-diseases-during-aging

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