The budding brain: How yeast give rise to treatments for neurodegenerative diseases

By Sara Wong

What do humans and baker’s yeast have in common? Surprisingly, they share a massive amount of genetic information and are governed by many of the same cellular processes. Although yeast do not have organs or limbs, they work like human cells and can be used to study a wide range of human diseases. Yeast are cheap, grow quickly, and are easily manipulated. These qualities allow scientists who study yeast to discover new genes and pathways relatively easily compared to other model organisms, like mice. One area of yeast research focuses on understanding neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease.

Neurodegenerative diseases: The unruly cling wrap of human health

Neurodegenerative diseases are commonly associated with protein aggregates, where certain proteins are not properly folded and stick to each other, forming clumps. For the cell, dealing with these protein aggregates is like a clumsy person trying to use cling wrap. They want to cover their leftover food, but instead, the cling wrap ends up sticking to itself, making it useless. They keep trying to pull more cling wrap off the roll – or in the cell’s case, make more protein – but it keeps sticking to itself. In the end, what’s left is a whole lot of unusable cling wrap and a dish of uncovered food. With protein aggregates, the proteins stick together in an unusable mess that the cell has to remove. Furthermore, whatever job the proteins normally perform goes undone. This combination can cause cellular stress and reduce its ability to function, since the cell is forced to use extra energy cleaning up the mess and compensate for the job left undone. When this occurs in neurons (cells in the brain that transmit information), it can cause or worsen neurodegenerative diseases.

Yeast as model organisms for diseased brains

Several labs have manipulated yeast to make protein aggregates, mimicking neurodegenerative disease. These yeast models are then used to make medical discoveries. For example, researchers wanted to find drugs that could help treat Parkinson’s disease, a neurodegenerative disease that affects movement and balance in over seven million people worldwide. To find treatments for Parkinson’s, researchers used yeast that make the alpha-synuclein aggregates associated with the disease. They then screened for drugs that prevented aggregate formation (1,2). Drugs that were able to get rid of protein aggregates in yeast are now being tested in mice with the hope that they will lead to treatment for human patients.

A similar approach was used to learn more about Amyotrophic Lateral Sclerosis (ALS), the neurodegenerative disease made famous by the Ice Bucket Challenge. Instead of looking for drugs that stopped aggregates from forming, the researchers wanted to look for cellular proteins that could affect the aggregates to understand the underlying cellular processes. ALS has been attributed to aggregation of a protein called TDP-43. Researchers created yeast that made TDP-43 aggregates and looked for proteins that, when absent, prevented the aggregates from forming. From this study, researchers found a protein called Dbr1, which helps degrade RNA. When Dbr1 is not expressed, RNAs were not degraded and instead bound to TDP-43, preventing TDP-43 aggregation. In this case, the RNA acted like a sponge to prevent TDP-43 protein aggregates. This research may lead to a novel treatment for ALS in which we can use RNA already found in the cell to prevent aggregation.

Letting yeast rise to their full potential

As you can see, something as seemingly simple (and distant from humans) as yeast can give rise to novel therapies for complex neurodegenerative diseases. Yet, the value of yeast research is not limited to this application. Several labs use yeast to study the process of how cells divide, with implications for cancer research. Yeast are also used to produce large quantities of high quality drugs, such as insulin.

The next time you enjoy a fresh loaf of bread and wash it down with a cold beer, remember that yeast do so much more than provide us with food and drink; yeast models help us understand the causes of disease, and allow researchers to find and develop improved therapies and treatments.

 About the author

swSara is a doctoral student at the University of Michigan in the Cell and Molecular Biology Program. She studies how the cell delivers cargoes to the correct place at the correct time. Sara was born and raised in New York City where she earned a BA in Biology from Macaulay Honors College at Queens College. Outside of lab, she enjoys running, painting, rock climbing, cooking, and petting her friends’ dogs.

Read all posts by Sara here.

 

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