Scientists at Scripps Research have discovered that a commonly-used antibiotic seems to help prevent the protein build-up associated with neurodegenerative diseases. In tests on roundworms, the researchers found that animals treated with the drug minocycline had less protein aggregation in their cells and subsequently lived longer.
Cells manufacture and dispose of proteins as part of their usual metabolism, and the amount of proteins in a healthy cell at any given time is relatively balanced – a state known as proteostasis. But one of the (many) downsides of aging is that this process eventually becomes unbalanced, leading to proteins accumulating inside cells. This is known as protein aggregation, and when it occurs in brain cells it's been associated with neurodegenerative diseases like Alzheimer's, Parkinson's and ALS.
Minocycline has long been thought to exhibit neuroprotective properties, but whether the antibiotic helped to clear out protein accumulation had never been specifically tested. That was the focus of this new study, using the roundworm species C. elegans.
"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 Gregory Solis, the study's lead author. "In this study, we investigated whether minocycline can reduce protein aggregation and extend lifespan in animals that already have impaired proteostasis."
To do so, the team treated groups of young and old worms with either minocycline or water as a control group. Then, they measured the levels of two proteins – α-synuclein, which is associated with Parkinson's disease, and amyloid-β, which seems to build up in patients with Alzheimer's. Sure enough, smaller amounts of both proteins built up in the worms treated with minocycline, in both the young and old animals, and lifespan increased as a result.
After further investigation, the team found that the antibiotic seems to directly regulate the ribosome, the molecular machinery in cells that synthesizes proteins. To put the link to the test, the team used worms that had been engineered to increase or decrease activity in the ribosome. Worms with lower protein production needed lower doses of minocycline to get the same benefits, and those that produced more needed higher doses.
"We have identified minocycline as a drug that can extend lifespan and improve protein balance in already-aging worms," says Michael Petrascheck, senior author of the study. "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."
As intriguing as the results are, and as much as everybody would like to live longer, it's important not to jump to conclusions too early. For starters, this study was conducted on worms, and the results won't necessarily carry across to humans. And minocycline has a few unfortunate side effects that might make scientists wary to prescribe it for long periods. A 2007 study found that the drug seems to speed up the rate of health decline in people with ALS, a neurodegenerative disease that's related to the ones that minocycline potentially helps.
Even if the drug itself isn't used in treatments, understanding the mechanism behind why it works could at least be explored in future studies.
The research was published in the journal eLife.
Source: Scripps Research
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