Mitoautophagy
Self-eating mitochondria may be the cause for amyotrophic lateral sclerosis
Scientists from Northwestern University have discovered a new phenomenon in the brain that can explain the development of early stages of neurodegeneration associated with impaired voluntary muscle movement, for example, when walking and talking, according to a press release from Northwestern University Self-cannibalizing mitochondria may set the stage for ALS development.
Article by Gautam et al. Mitoautophagy: A Unique Self-Destructive Path Mitochondria of Upper Motor Neurons With TDP-43 Pathology Take, Very Early in ALS published in the journal Frontiers in Cellular Neuroscience – VM.
The discovery was so groundbreaking that scientists needed to come up with a new term to describe it: mitoautophagy – a set of self-destructing mitochondria in the affected upper motor neurons of the brain, which begin to disintegrate from the inside at a very early age. The upper motor neurons in the brain are responsible for the onset of muscle movement and relaxation and are among the first to disrupt functioning in neurodegenerative diseases.
This phenomenon is observed mainly in one of the most common pathologies in neurodegenerative diseases – TDP-43 pathology, which is observed in more than 90% of cases of amyotrophic lateral sclerosis (ALS).
"I think we've found the culprit for why primary neurons become vulnerable to future degeneration: suicidal mitochondria," said senior study author Hande Ozdinler, associate professor of neurology at Northwestern University School of Medicine. Feinberg. – Mitochondria, as a rule, eat themselves very early in the development of the disease. This happens selectively in neurons that rapidly degenerate in the patient's brain."
"This type of degeneration starts much earlier than previously thought," says the study's lead author Mukesh Gautam.
Using a process called immune-linked electron microscopy, the scientists investigated cellular events that go wrong inside neurons vulnerable to disease. After analyzing more than 200 neurons, they observed the self-destruction of mitochondria only in the affected neurons, and especially in the context of TDP-43 pathology.
Mitochondria are the engines of a cell that create and maintain energy in cells. In the affected upper motor neurons, the mitochondria first self-destruct by elongation, then form a ring-shaped structure until they finally disintegrate from the inside.
This type of degeneration has never been observed before, and it differs from the previously described stages of mitochondrial degeneration.
The study analyzed mitochondria in the upper motor neurons of three different ALS models in mice aged 15 days. Ozdinler and her team have shown many times that the upper neurons, even in different species, are almost identical at the cellular level, especially in the context of TDP-43 pathology.
"These self–destructing mitochondria may become a future target for drug therapy in the treatment of ALS and other neurodegenerative diseases in which human movements are affected," Ozdinler said. They are currently working with pharmaceutical companies to find out if the drugs used for patients with mitochondrial disease can actually improve the condition of motor neurone patients.
"Many drugs that are currently on the market and target the health and integrity of mitochondria may well be reused 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 stability of mitochondria. If we improve mitochondrial health early, we can even eliminate the formation of protein aggregates – a pathology widely observed in many diseases."
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