Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 35

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"Their mitochondria, the cellular powerhouses, weren't working as well at the neurite
ends," said Dr. Baranov. Then, when the researchers looked at neurons in the spinal
cords of mice, they found the same phenomenon. "Other researchers must have
noticed this as well, but we were able to visualize it and suggest the potential cause as
well as outcome," he noted.
The researchers found that when proteins in mitochondria at the ends of neurites were
damaged by normal wear and tear, newer ones weren't coming in to replace them as
quickly as they did for mitochondria near the nucleus. This made them function less
efficiently, which activated "executioner" enzymes called caspases and ultimately led
to neurites withering away.
Dr. Friedlander and his team called this neuritosis, a variation on apoptosis, the cell
death process that involves caspase activation. "It's quite intuitive, once we discovered
how it works," said Dr. Friedlander. "Neuronal projections are really long and the farther
you are from the nucleus, which is the central factory, the harder it gets to repair and
replenish the cellular machinery, making the ends more vulnerable to even small
stresses."
The researchers then wanted to understand whether neuritosis plays a role in neurodegenerative disease, and they had reason to suspect that it does. Previous work
in Dr. Friedlander's lab showed that mutations in huntingtin, the protein linked to
Huntington's disease, interferes with the same protein supply chain that breaks down
in neuritosis.
To test their hunch, Dr. Friedlander's team used genetically modified mice that carried
a mutant version of the human huntingtin protein. These mice exhibit symptoms of
the disease, including accelerated neuronal death. Their findings were similar to what
they had seen in the cells, but more pronounced. There were fewer mitochondria at
the ends, and what remained was more dysfunctional than in normal neurons. There
was also more activation of caspases, and increased levels of cell death.
"It's quite likely that neuritosis happens in nerve cells normally and doesn't result in
cell death, but in neurodegenerative diseases. There are higher levels of stress to the
already vulnerable neurite ends, which could push neuritosis over the edge and lead to
cells dying," said Dr. Friedlander. "If we can somehow find a way to keep mitochondria at
n
nerve ends healthy, it may be beneficial in treating neurodegenerative diseases."	
35

| January, 2019

Dr. Friedlander
and his team called
this neuritosis,
a variation on
apoptosis, the cell
death process that
involves caspase
activation.


http://www.genengnews.com

Gain Critical Insights from Advanced Cell Models with Real-Time Analysis

Table of Contents for the Digital Edition of Gain Critical Insights from Advanced Cell Models with Real-Time Analysis

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Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 1
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - Contents
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 3
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 4
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 5
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 6
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 7
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 8
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 9
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 10
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 11
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 12
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 13
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 14
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 15
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 16
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 17
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 18
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 19
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 20
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 21
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 22
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 23
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 24
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 25
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 26
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 27
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 28
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 29
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 30
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 31
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 32
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 33
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 34
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 35
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