Proteins last longer in the brain

Study in mice could shed light on aging, Alzheimer’s

When it comes to proteins’ shelf lives, where they’re stored matters. In mice, proteins stick around over twice as long in the brain as they do in the liver and blood, a study appearing in an upcoming issue of the Proceedings of the National Academy of Sciences finds.

To keep the body and brain on track, cells constantly make and destroy proteins. Hiccups in this cycling process can have serious consequences, particularly in the brain. The new study, which was done using tissues in live animals rather than cells in a dish, gives researchers a better feel for proteins’ life-spans in an actual animal, which may lead to a better understanding of aging and diseases such as Alzheimer’s and Parkinson’s.

To keep tabs on protein longevity, coauthor Sina Ghaemmaghami of the Institute for Neurodegenerative Diseases at the University of California, San Francisco and his colleagues fertilized a big batch of spirulina — the high-protein blue-green algae found in health nuts’ smoothies — in the presence of a trackable heavy isotope of nitrogen and then fed the doped food to mice. As soon as the mice ate the spirulina, their cells began weaving the heavy nitrogen into all of the freshly made proteins throughout their bodies. Comparing the amounts of normal and heavy nitrogen in particular proteins told the researchers how much protein had been made since the spirulina diet had begun.

The researchers collected three different tissues from the mice — brains, liver and blood — at time points ranging from less than a day to over one month after feeding spirulina to the animals, then tallied how long proteins stuck around in each bodily locale.

Proteins’ lifespans varied widely, the team found. Overall, some proteins were estimated to completely turn over in just minutes, and for proteins involved in sending signals between cells and helping other proteins fold, completely new pools of proteins were apparent in hours. Other proteins, such as those that help package DNA and those that help maintain neurons, were estimated to stick around for up to a year.

When the team compared protein turnover among tissues, they found that on average, proteins in the brain lasted for nine days, while those in the liver and blood disappeared after about three days. In cases where the same protein was present in both the brain and the liver, the brain-dwelling protein outlasted the one in the liver without exception.

The new study also highlights the differences between protein turnover in live animals and what happens in lab experiments using cells in a dish. Proteins turned over much faster in experiments on collections of human cells in lab dishes, earlier studies found, suggesting that proteins behave differently when they are operating in complicated tissues.

“In a complex organism, there are a lot more different factors that influence how fast proteins turn over,” says Ghaemmaghami. Studies like this offer a more realistic view of the cells’ behavior, he says.

The new study’s results are interesting, but the key value of the work is that it will allow scientists to start looking at protein turnover malfunctions in animals with versions of neurodegenerative diseases that are marked by protein aggregations, such as Alzheimer’s and Parkinson’s, says neuroscientist Maja Bresjanac of the University of Ljubljana in Slovenia. 

Knowing how proteins are created and destroyed in these animals — particularly in the brain — may lead to a deeper understanding of what happens during aging and in diseases caused by errant proteins sticking around too long.

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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