Rare childhood disease may hold clues to treating Alzheimer's and Parkinson's

October 27, 2013

Scientists at Rutgers University studying the cause of a rare childhood disease that leaves children unable to walk by adolescence say new findings may provide clues to understanding more common neurodegenerative diseases like Alzheimer's and Parkinson's and developing better tools to treat them.

In today's online edition of Nature Neuroscience, professors Karl Herrup, Ronald Hart and Jiali Li in the Department of Cell Biology and Neuroscience, and Alexander Kusnecov, associate professor in behavioral and systems neuroscience in the Department of Psychology, provide new information about A-T disease, a rare genetic childhood disorder that occurs in an estimated 1 in 40,000 births.

Children born with A-T disease have mutations in both of their copies of the ATM gene and cannot make normal ATM protein. This leads to problems in movement, coordination, equilibrium and muscle control as well as a number of other deficiencies outside the nervous system.

Using mouse and human brain tissue studies, Rutgers researchers found that without ATM, the levels of a regulatory protein known as EZH2 go up. Looking through the characteristics of A-T disease in cells in tissue culture and in brain samples from both humans and mice with ATM mutation, they found that the increase in EZH2 was a major contributing factor to the neuromuscular problems caused by A-T.

"We hope that this work will lead to new therapies to prevent symptoms in those with A-T disease," says Hart. "But on a larger level, this research provides a strong clue toward understanding more common neurodegenerative disorders that may use similar pathways. "It is a theme that has not yet been examined."

While the EZH2 protein has been shown to help determine whether genes get turned on or off, altering the body's ability to perform biological functions, necessary for maintaining good health, the Rutgers study is the first time this protein -- which can cause adverse health effects if there is too much of it -- has been looked at in the mature nerve cells of the brain.

By reducing the excess EZH2 protein that accumulated in mice genetically engineered with A-T disease, and creating a better protein balance within the nerve cells, Rutgers scientists found that mice exhibited improved muscle control, movement and coordination.

In the study, mutant mice that had A-T disease and increased levels of EZH2 were "cured" when this excess EZH2 protein was reduced. The treated mice were able to stay on a rotating rod without falling off almost as long as the mice that did not have A-T disease. By contrast, untreated A-T animals lost their balance and fell off the device almost immediately. The mice were also studied in an open area setting. While the treated A-T mice and normal mice explored a wide area of the open field, the A-T mice, with their excess EZH2 protein, were not as adventurous and stayed behind.

Rutgers scientists say the implications of these findings now need to be validated in a clinical setting. They have begun working with the A-T Clinical Center at Johns Hopkins University, collecting blood samples from children with the disease as well as their parents who carry the genes in order to reprogram them into stem cells. This will allow scientists to create human neurons like those in A-T patients and study the mechanisms that lead from ATM mutations to nerve cell disease in more detail.

The hope is that this new information can be used to develop therapeutic drugs that may result in better neuromuscular control and coordination for those with A-T disease. In addition, the scientists will work to determine whether the EZH2 protein plays a role in other more common neurodegenerative diseases, like Parkinson's and Alzheimer's and could offer a target for developing drugs to treat those brain disorders.

"What is interesting about human health and this research in particular is that it illustrates how a disease that is thought of as 100 percent genetic, actually has a component that is sensitive to the environment," says Herrup, lead author of the study.
-end-


Rutgers University

Related Nerve Cells Articles from Brightsurf:

Nerve cells let others "listen in"
How many ''listeners'' a nerve cell has in the brain is strictly regulated.

Nerve cells with energy saving program
Thanks to a metabolic adjustment, the cells can remain functional despite damage to the mitochondria.

Why developing nerve cells can take a wrong turn
Loss of ubiquitin-conjugating enzyme leads to impediment in growth of nerve cells / Link found between cellular machineries of protein degradation and regulation of the epigenetic landscape in human embryonic stem cells

Unique fingerprint: What makes nerve cells unmistakable?
Protein variations that result from the process of alternative splicing control the identity and function of nerve cells in the brain.

Ragweed compounds could protect nerve cells from Alzheimer's
As spring arrives in the northern hemisphere, many people are cursing ragweed, a primary culprit in seasonal allergies.

Fooling nerve cells into acting normal
In a new study, scientists at the University of Missouri have discovered that a neuron's own electrical signal, or voltage, can indicate whether the neuron is functioning normally.

How nerve cells control misfolded proteins
Researchers have identified a protein complex that marks misfolded proteins, stops them from interacting with other proteins in the cell and directs them towards disposal.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Research confirms nerve cells made from skin cells are a valid lab model for studying disease
Researchers from the Salk Institute, along with collaborators at Stanford University and Baylor College of Medicine, have shown that cells from mice that have been induced to grow into nerve cells using a previously published method have molecular signatures matching neurons that developed naturally in the brain.

Bees can count with just four nerve cells in their brains
Bees can solve seemingly clever counting tasks with very small numbers of nerve cells in their brains, according to researchers at Queen Mary University of London.

Read More: Nerve Cells News and Nerve Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.