The antibiotic minocycline increases the lifespan of aged roundworms and prevents the buildup of proteins, revealing a protective mechanism that could be exploited therapeutically to help prevent neurodegenerative diseases.
Now, scientists at Scripps Research have found that minocycline can increase the lifespan of roundworms by preventing the buildup of proteins during aging, according to a study in the open-access journal eLife reports.
Protein aggregation causes several progressive age-related brain diseases, including amyotrophic lateral sclerosis, Alzheimer’s, Parkinson’s and prion diseases. The Scripps Research study shows that minocycline prevents this buildup even in older animals with age-impaired stress-response pathways.
The number of proteins in a cell is balanced by the rate of protein manufacture and disposal, called proteostasis. As we age, proteostasis becomes impaired.
“It would be great if there were a way to enhance proteostasis and extend lifespan and health, by treating older people at the first sign of neurodegenerative symptoms or disease markers such as protein build-up,” says lead author Gregory Solis, a graduate student at Scripps Research. “In this study, we investigated whether minocycline can reduce protein aggregation and extend lifespan in animals that already have impaired proteostasis.”
The team first tested 21 different molecules known to extend lifespan in young and old Caenorhabditis elegans (C. elegans) worms. They found that all of these molecules prolonged the lives of young worms, however, the only drug that worked on the older worms was minocycline.
To find out why, the researchers looked at whether minocycline had any effect on protein aggregation in the worms. They treated young and old worms with water or minocycline and then measured two proteins, ?-synuclein and amyloid-?, which are known to build up in Parkinson’s and Alzheimer’s, respectively. Regardless of the worms’ age, those treated with minocycline had reduced aggregation of both proteins as they grew older.
The team next turned their attention to the mechanism behind this discovery. First, they looked at whether minocycline switches on stress-signaling proteins that are impaired in older worms, but they found the drug actually reduces their activity. Next, they studied whether it turns off the cell’s protein-disposal processes, but this was not its mode of action either.
When researchers used a chemical probe to see how minocycline affects the major protein-regulating molecules in the cell, it revealed that minocycline directly affects the protein-manufacturing machinery of the cell, known as the ribosome. This was true in worms, as well as in mouse and human cells.
Finally, the team used worms with increased or decreased protein-manufacturing activity and studied how this altered the effect of minocycline on protein levels and lifespan. As predicted, in mutant worms where protein manufacturing was already decreased, they found a lower dose of minocycline was needed to further reduce protein levels and extend lifespan. In worms where protein manufacturing was increased, the opposite was seen. This suggested that minocycline extends lifespan by controlling the rate of protein manufacturing at the ribosome.
“We have identified minocycline as a drug that can extend lifespan and improve protein balance in already-aging worms,” says Michael Petrascheck, PhD, senior author of the paper and associate professor at Scripps Research. “Our study reveals how minocycline prevents protein aggregation and lays the foundations for drug development efforts aimed at optimizing this already-approved drug for a range of neurodegenerative diseases.”
The Latest on: Minocycline
via Google News
The Latest on: Minocycline
- An Open-label Pilot Trial of Minocycline in Children as a Treatment for Angelman Syndromeon January 13, 2021 at 4:00 pm
Since no previous research existed showing how children with AS would respond to minocycline, statistical methods could not be employed to determine sample size. Therefore, human subject ...
- An Open-label Pilot Trial of Minocycline in Children as a Treatment for Angelman Syndromeon January 12, 2021 at 3:59 pm
Background Minocycline, a member of the tetracycline family, has a low risk of adverse effects and an ability to improve behavioral performance in humans with cognitive disruption. We performed a ...
- Global Minocycline Hydrochloride Industry Market Experiments, Evolution and Forecast Till 2026on December 30, 2020 at 12:51 am
Pune, Maharashtra, India, December 30 2020 (Wiredrelease) MarketDesk –:The in-depth analysis study on Global Minocycline Hydrochloride Industry Market serves latest business data and advanced ...
- VYNE Therapeutics Announces New U.S. Patent Expiring in 2037 for AMZEEQ® (minocycline) topical foam, 4%on December 15, 2020 at 12:00 am
“We continue to develop, extend and consolidate our robust patent portfolio and are pleased with the addition of this new patent, which provides further coverage for our novel topical ...
- Preventing Complications of Central Venous Catheterizationon August 14, 2020 at 8:34 pm
10 Current evidence suggests that minocycline-and-rifampin–impregnated catheters are even more effective for minimizing the risk of infection than those that are impregnated with chlorhexidine ...
- Minocycline HCL ERon August 12, 2020 at 8:02 pm
Read the Patient Information Leaflet if available from your pharmacist before you start taking minocycline and each time you get a refill. If you have any questions, ask your doctor or pharmacist.
- Minocycline 4 % Topical Foamon January 19, 2020 at 2:52 am
Read the Patient Information Leaflet and Instructions for Use provided by your pharmacist before you start using minocycline foam and each time you get a refill. If you have any questions ...
- Minocycline Topical Foam to be Available in Pharmacies Starting January 13on January 9, 2020 at 1:03 pm
Minocycline topical foam, 4% (Amzeeq, Foamix) will be available by prescription for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in adults and pediatric ...
- Treating 'Fragile X Syndrome' autism symptomson January 3, 2019 at 6:49 pm
As part of a clinical trial, Holly started taking a serotonin medication. Then, minocycline, a common antibiotic normally used to treat acne, was added to her regimen. "Her developmental testing ...
- Injectable Hydrogel Delivering Therapeutic Levels of Minocycline to Reduce the Secondary Injury Process of Spinal Cord Injurieson October 8, 2018 at 7:47 pm
Following SCI, the lesion expands greatly over time due to a wave of secondary injury processes. Minocycline (MH) is a clinically available drug that has been shown to target almost all secondary ...
via Bing News