Nav: Home

Molecular bodyguards against Parkinson's disease

December 04, 2019

Chaperone proteins in human cells dynamically interact with the protein α-Synuclein, which is strongly associated with Parkinson's disease. A disturbed relationship to these "bodyguards" leads to cell damage and the formation of Lewy bodies typical for Parkinson's disease. The findings by researchers from the University of Basel's Biozentrum have been published in "Nature".

Parkinson's disease is one of the most common neurodegenerative disorders. In Switzerland, about 15,000 people are affected. Because of the worldwide rise in life expectancy, a rapid increase in Parkinson's cases is expected in the next years. The causes of the disease, which leads to the progressive death of nerve cells in the brain, are still not well understood. Therefore, the development of effective therapies is all the more difficult.

It is well accepted that the protein α-Synuclein can play a key role in the development of Parkinson's. Researchers led by structural biologist Prof. Sebastian Hiller have now discovered that assisting proteins, known as chaperones, are constantly protecting α-Synuclein in human cells. Whenever the chaperones are unable to fulfill their bodyguard job, α-Synuclein shows its negative side and causes serious cell damage.

Molecular bodyguards interact with α-Synuclein

In human cells, there are about thirty to forty chaperones that can potentially interact with α-Synuclein. The scientists have systematically investigated at the atomic level where the molecular bodyguards interact with α-Synuclein.

"Using state-of-the-art NMR technology, we have discovered a specific pattern that determines the exact interaction site of α-Synuclein with chaperones," explains Hiller. "There is not fixed, rigid interaction, but a dynamic and constantly changing encounter." In healthy cells, α-Synuclein is always accompanied by chaperones such that the protein remains transportable and at all times a pool of functional α-Synuclein proteins is available.

Impaired chaperone binding causes cell damage

There are serious consequences if the chaperones are no longer able to perform their bodyguard function. Chemical modifications of α-Synuclein, such as those observed in Parkinson's disease, interfere with chaperone binding. These "unaccompanied" α-Synuclein proteins can re-localize and accumulate on the membrane of mitochondria, the power plants of the cell, and gradually destroy them. As recently shown, Lewy bodies typical for Parkinson's disease mainly consist of mitochondrial membrane fragments and α-Synuclein.

New function for chaperones discovered

"With our work, we are questioning the paradigm that the function of chaperones is solely to help proteins to fold into their proper shape," says Hiller. "Chaperones do far more than just assist in protein folding. They control cellular processes by flexibly interacting with a variety of proteins and accompanying them like a shadow."

Understanding the molecular interactions and the interactions between the partners involved provides important clues for the treatment of Parkinson's disease. In the future, chaperones and the maintenance of their function should also be considered in the development of novel therapies.
-end-


University of Basel

Related Proteins Articles:

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.
New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.
Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.
Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.
Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.
Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.
Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.
Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.
How proteins become embedded in a cell membrane
Many proteins with important biological functions are embedded in a biomembrane in the cells of humans and other living organisms.
Finding the proteins that unpack DNA
A new method allows researchers to systematically identify specialized proteins called 'nuclesome displacing factors' that unpack DNA inside the nucleus of a cell, making the usually dense DNA more accessible for gene expression and other functions.
More Proteins News and Proteins Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.