Scientists uncover cell mechanism that plays key role in ALS

Date: Jan-29-2015 Scientists have discovered a mechanism that causes defects in a group of brain

cells that is key to the development of ALS, or Lou Gehrig's disease. The researchers hope

the discovery will lead to a new target for treating this and other neurodegenerative

diseases that may share a similar cause.

ALS is a disease that gradually destroys brain cells that control muscle movement.

The team, led by Hande Ozdinler, assistant professor in the Ken and Ruth Davee

Department of Neurology at Northwestern University in Chicago, IL, reports the findings in

the journal Cerebral Cortex.

Amyotrophic lateral sclerosis (ALS) first came to public attention when an American

baseball player called Lou Gehrig died of the disease in 1941.

ALS is a disease that gradually destroys motor neurons - the brain cells that control muscle

movement - leading to increasing muscle weakness, impaired speech, problems with swallowing

and breathing, and eventually paralysis and death.

ALS progresses at different speeds in different people - the average life expectancy

after diagnosis is between 2 and 5 years.

Study explains why upper motor neurons are vulnerable to degeneration

In earlier work, Prof. Ozdinler had established the important role of upper motor

neurons - a small group of neurons in the brain - in the development of ALS.

In this latest study, the team begins to explain why this group of neurons - which

makes up only about 150,000 of the 2 billion cells in the brain - is vulnerable to

degeneration.

They developed a new mouse model for studying upper motor neurons, and found that

increasing stress in the endoplasmic reticulum (ER) is one cause of upper motor neuron death.

The ER is a cell component that serves as a site for making proteins and lipids.

The new model is a breed of mice that lack the UCHL1 gene. Previous studies have linked

mutations in this gene to motor defects in human patients. Using cell cultures and the new

mouse model, the team found that loss of UCHL1 protein function affects protein regulation

pathways, ER stress and upper motor neuron survival.

Commenting on the finding, Prof. Ozdinler says:

"Now that we appreciate the importance of upper motor neurons, we need to develop

therapies that improve their survival. This study gives us a target to go after, bringing

us one step closer to building effective treatment strategies."

Findings could have implications for Parkinson's, Alzheimer's

Prof. Ozdinler says while other types of brain cell vastly outnumber upper motor

neurons, their function is vital. She explains:

"They act as the spokesperson of the brain by collecting, integrating, translating and

transmitting the brain's message to the spinal cord targets, and by doing so they initiate and

modulate voluntary movement."

Previously, scientists believed spinal motor neurons were more important in ALS and that

upper motor neurons played a secondary role.

The team believes the findings could also have applications to other neurodegenerative

diseases partly caused by ER stress, including Parkinson's disease and Alzheimer's disease.

ALS was in the headlines more recently when videos of the ALS Association's Ice Bucket

Challenge went viral on the internet in 2014. And in the more recent release of the film The

Theory of Everything, we saw how physicist and cosmologist Stephen Hawking - who has been

living with ALS for 50 years - and his wife met the challenges in the early years.

Another theory of how ALS develops is the framework destabilization hypothesis. This

proposes the disease is triggered when the clean-up process inside brain cells cannot keep

up with the rate at which waste is generated.

In October 2014, Medical News Today learned how increased protein instability may be a cause of ALS. The

researchers found different mutations in a particular gene - SOD1 - might cause

instability in SOD proteins, meaning they cannot fold properly and accumulate in brain cells

faster than the clean-up process can cope with.

Written by Catharine Paddock PhD

Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.