Nav: Home

Self-cannibalizing mitochondria may set the stage for ALS development

November 07, 2019

CHICAGO --- Northwestern Medicine scientists have discovered a new phenomenon in the brain that could explain the development of early stages of neurodegeneration that is seen in diseases such as ALS, which affects voluntary muscle movement such as walking and talking. 

The discovery was so novel, the scientists needed to coin a new term to describe it: mitoautophagy, a collection of self-destructive mitochondria in diseased upper motor neurons of the brain that begin to disintegrate from within at a very early age. Upper motor neurons in the brain are responsible for initiating muscle movement and relaxation and are one of the first to break down in neurodegenerative diseases.

The study will be published on November 7 in the journal Frontiers in Cellular Neuroscience.

The phenomenon is observed mainly in one of the most common pathologies observed in neurodegenerative diseases, TDP-43 pathology, which is seen in more than 90% of ALS cases. When a pathology is present in the body, it indicates that something is wrong or functioning abnormally.

"I think we have found the culprit that primes neurons to become vulnerable to future degeneration: suicidal mitochondria," said senior study author Hande Ozdinler, associate professor of neurology at Northwestern University Feinberg School of Medicine. "The mitochondria basically eat themselves up very early in the disease. This occurs selectively in the neurons that will soon degenerate in patient's brains."

"This type of degeneration begins much earlier than previously thought," said study lead author Mukesh Gautam, the A Long Swim (ALS) Ellen Blakeman fellow at Northwestern.

Using a process called immuno-coupled electron microscopy, the scientists investigated the cellular events that go wrong inside the neurons that become vulnerable to disease. After analyzing more than 200 neurons, they observed the self-destruction of mitochondria only in the diseased neurons, and especially within the context of TDP-43 pathology.  

Mitochondria are powerhouses of the cell that create and maintain energy in the cells. In the diseased upper motor neurons, mitochondria self-destruct first by elongating, then forming a ring-like structure, until they finally disintegrate from the inside out. 

It is a type of degeneration never been seen before, and it is different from previously described stages of mitochondrial degeneration. 

The study analyzed mitochondria in the upper motor neurons of three different mouse models of ALS at only 15 days old - equivalent to a toddler in humans. While the study was in mice, Ozdinler and her team showed many times before that the upper neurons even in different species are almost identical at a cellular level, especially within the context of TDP-43 pathology. 

These self-destructive mitochondria could become a future target for drug therapies to treat ALS and other neurodegenerative diseases in which a person's movement is affected, Ozdinler said. They are currently working with drug companies to see if drugs used for human patients with mitochondrial disease could in fact improve the health of diseased motor neurons.

"Many of the drugs currently on the market that target the health and the integrity of mitochondria may well be repurposed and considered for neurodegenerative diseases in the future," Ozdinler said. "Maybe we don't need to reinvent the wheel to cure ALS and other neurodegenerative diseases.

"To overcome neurodegeneration, we need to improve the health and the stability of mitochondria. If we improve the health of the mitochondria early, we may even eliminate protein aggregate formation, a pathology broadly observed in many diseases." 
-end-
Edward Xie and Nuran Kocak, both from Northwestern, are co-authors on the paper. 

The research was supported by the Les Turner ALS Foundation and the National Institutes of Health.

Northwestern University

Related Neurons Articles:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.
Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.
A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.
Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.
Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.
Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.
The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.
Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.
How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.
A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.
More Neurons News and Neurons 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: IRL Online
Original broadcast date: March 20, 2020. Our online lives are now entirely interwoven with our real lives. But the laws that govern real life don't apply online. This hour, TED speakers explore rules to navigate this vast virtual space.
Now Playing: Science for the People

#573 Penis. That's It. That's the title.
This episode is about penises. That was your content warning. Penises. Where they came from. Why they're useful. And the many, many wild things that animals do with them. Come for the world's oldest penis, stay for the creature that ejaculates 80 percent of its bodyweight. Host Bethany Brookshire talks with Emily Willingham about her new book, "Phallacy: Life Lessons from the Animal Penis".
Now Playing: Radiolab

Falling
There are so many ways to fall–in love, asleep, even flat on your face. This hour, Radiolab dives into stories of great falls.  We jump into a black hole, take a trip over Niagara Falls, upend some myths about falling cats, and plunge into our favorite songs about falling. Support Radiolab by becoming a member today at Radiolab.org/donate.