Nav: Home

Study provides understanding of how nerve cells are damaged by accumulation of abnormal proteins

May 25, 2017

(Boston)--A new study has uncovered a molecular mechanism in the prion protein, a protein responsible for neurodegenerative diseases, which may explain why nerve cells degenerate in these disorders.

The findings, which appear in the journal eLife, may one day lead to better therapies and treatments for these diseases.

The prion protein plays a crucial role in fatal neurodegenerative disorders like Creutzfeldt-Jakob disease in humans and "mad cow disease" in cattle. Prion diseases are part of larger group of human neurodegenerative disorders, including Alzheimer's, Parkinson's and Huntington's diseases, which are all due to the abnormal accumulation of protein aggregates in the brain.

According to the researchers, how nerve cells are damaged in these diseases has remained a mystery until now. "Our work shows that the prion protein acts like a molecular on-off switch. In the "on" positon, one end of the protein delivers a toxic signal to nerve cells, while in the "off" position, the other end of the protein serves as a brake to reduce the toxic signal. Moreover, copper, a metal that is a normal component of brain biochemistry, biases the prion protein towards the "off" state. This novel mechanism, in which the two parts of the prion protein have opposing functions, had not been fully appreciated before," explained corresponding author David Harris, MD, PhD, professor and chair of the department of biochemistry at Boston University School of Medicine (BUSM).

Using a multi-disciplinary approach involving electrophysiological, cellular and biophysical techniques, the researchers found that parts of the prion protein lacking the "brake" region produced abnormal electrical currents in cells. Antibodies that interfered with the functioning of the brake region did the same. Importantly, the antibody treatment also caused severe degeneration of nerve cell dendrites, the regions that are essential for normal communication between nerve cells. In collaboration with colleagues at the University of California (UC), Santa Cruz, the researchers applied a sophisticated chemical technique to demonstrate that the two ends of the prion protein interact with each to alter the amount of toxic signal that is delivered.

As a result of their findings, the researchers caution against administering antibodies against the prion as a possible therapy for both prion and Alzheimer's diseases. "Our study sounds a serious warning about the possible detrimental side effects of this strategy, since we have shown that such antibodies cause dramatic degeneration of nerve cells by interfering with the normal on-off function of the prion protein," he added.

The researchers hope their study will lead to better therapies for neurodegenerative disorders, as well as help clinicians avoid the possible dangerous side-effects of using anti-prion protein antibodies for therapeutic purposes. "These data provide the best picture yet of the prion protein's 'off state,'" said coauthor Glenn Millhauser, PhD, from UC Santa Cruz. "Recognizing the nature of this state provides a platform for developing drugs to treat neurodegenerative diseases. This is an exciting time in prion biology."
-end-
Funding for this study was provided by the National Institutes of Health (grants R01 NS065244 to D.A.H.; R01 GM065790 to G.L.M., and GM104316 to D.W.C.; the National Science Foundation (grant 1454508 to D.W.C.) and by funds from the German Research Foundation (TA 167/6) to J.T.

Boston University Medical Center

Related Nerve Cells Articles:

Unique fingerprint: What makes nerve cells unmistakable?
Protein variations that result from the process of alternative splicing control the identity and function of nerve cells in the brain.
Ragweed compounds could protect nerve cells from Alzheimer's
As spring arrives in the northern hemisphere, many people are cursing ragweed, a primary culprit in seasonal allergies.
Fooling nerve cells into acting normal
In a new study, scientists at the University of Missouri have discovered that a neuron's own electrical signal, or voltage, can indicate whether the neuron is functioning normally.
How nerve cells control misfolded proteins
Researchers have identified a protein complex that marks misfolded proteins, stops them from interacting with other proteins in the cell and directs them towards disposal.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
Research confirms nerve cells made from skin cells are a valid lab model for studying disease
Researchers from the Salk Institute, along with collaborators at Stanford University and Baylor College of Medicine, have shown that cells from mice that have been induced to grow into nerve cells using a previously published method have molecular signatures matching neurons that developed naturally in the brain.
Bees can count with just four nerve cells in their brains
Bees can solve seemingly clever counting tasks with very small numbers of nerve cells in their brains, according to researchers at Queen Mary University of London.
Nerve cells in the human brain can 'count'
How do we know if we're looking at three apples or four?
How rabies virus moves through nerve cells, and how it might be stopped
Researchers found that the rabies virus travels through neurons differently than other neuron-invading viruses, and that its journey can be stopped by a drug commonly used to treat amoebic dysentery.
Direct conversion of non-neuronal cells into nerve cells
Researchers of the Mainz University Medical Center discovered that on the way to becoming neurons pericytes need to go through a neural stem cell-like state.
More Nerve Cells News and Nerve Cells 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

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.