CHICAGO, Nov. 9 (Xinhua) -- Researchers at Northwestern Medicine have discovered a new phenomenon in the brain that could explain the development of early stages of neurodegeneration seen in diseases such as ALS, which affects voluntary muscle movement such as walking and talking.
They invented a new term to describe the discovery: 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.
Using a process called immuno-coupled electron microscopy, the researchers 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, which is seen in more than 90 percent of ALS cases.
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.
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.
"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 (NU) 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 Ellen Blakeman fellow at NU.
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, said Ozdinler.
The study was published on Thursday in the journal Frontiers in Cellular Neuroscience.
Northwestern Medicine is the collaboration between Northwestern Memorial Healthcare and Northwestern University Feinberg School of Medicine, which encompasses research, teaching and patient care activities.
