OCT 02, 2019 4:17 PM PDT

Gaining New Insight Into ALS and Other Neurodegenerative Disorders

WRITTEN BY: Carmen Leitch

Dementia and Alzheimer’s disease were once thought to be very closely related, but scientists reported earlier this year that a variety of processes can cause dementia. It helps to explain why not everyone with Alzheimer’s has a buildup of tau or amyloid plaques that were considered a feature of the disease, and why treatments aimed at these plaques haven't worked. Researchers described a new kind of dementia earlier this year, called LATE.

Image credit: Pixabay

"Recent research and clinical trials in Alzheimer's disease have taught us two things: First, not all of the people we thought had Alzheimer's have it; second, it is very important to understand the other contributors to dementia," said Nina Silverberg, Ph.D., director of the Alzheimer's Disease Centers Program at National Institute on Aging (NIA).

Several years ago, scientists began to recognize that another protein, TDP-43, may be involved in neurodegeneration. The TDP-43 (transactive response DNA binding protein) molecule normally plays a role in helping cells to make proteins. Proteins are made of strings of amino acids that have to be carefully folded into their correct structure to be functional. When the TDP-43 protein is not folded correctly, it leaves its normal cellular location.

Dysfunctional TDP-43 has been implicated in another devastating neurodegenerative disorder affecting the brain and spinal cord, amyotrophic lateral sclerosis (ALS), though it's not known whether the protein dysfunction is a cause, or if it arises after the disease begins.

Scientists at the Center of Genomic Regulation (CRG) and the Institute of Bioengineering of Catalonia (IBEC) have now used a technique called deep mutagenesis to reveal more. They systematically introduced errors into the TDP-43 protein to see what the effects were. The findings have been reported in Nature Communications.

"By studying all possible mutations in a protein, we have a much more reliable way to understand toxicity, and we are excited to move on to many more proteins implicated in neurodegenerative diseases," explained the first author of the study, Benedetta Bolognesi, an IBEC researcher.

The scientists engineered 50,000 TDP-43 yeast cell mutants. They found that TDP-43 mutants that clumped together as seen in the disease were actually less toxic to cells than mutants that created liquid-like forms that condensed.

"This is the exact opposite of what we expected," noted Lehner. This work can change what we thought about neurodegenerative diseases.

Bolognesi’s team wants to know more about whether the accumulation of TDP-43 has a protective impact on neurons. If that is the case, it may fundamentally change treatment approaches.

Learn more about LATE (limbic-predominant age-related TDP-43 encephalopathy) from the video.


Sources: University of Kentucky, CRG, Brain, Nature Communications

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
APR 13, 2020
Cell & Molecular Biology
APR 13, 2020
Getting Closer to Making Heparin in Cells
While heparin is the most commonly prescribed drug in hospitals, we have to extract it from pig intestines, which is fra ...
APR 28, 2020
Genetics & Genomics
APR 28, 2020
Evolution Observed in Fish in a Single Generation
In a five year study, scientists have now shown that stickleback fish were able to alter some of their traits within a s ...
MAY 06, 2020
Genetics & Genomics
MAY 06, 2020
Advances in Genome Sequencing Technology
We've come a long way from the human genome project, which took years to complete. It now takes about 6 hours to sequenc ...
MAY 19, 2020
Genetics & Genomics
MAY 19, 2020
A Faster Way to Identify New Cell Types
It's important to be able to identify the types of cells that are present in a tissue and how they behave in order to ha ...
MAY 29, 2020
Genetics & Genomics
MAY 29, 2020
Advances in Our Understanding of Huntington's Disease
Huntington's disease (HD) is a fatal neurodegenerative disease caused by an expanded sequence in the huntingtin gene.
JUN 20, 2020
Cancer
JUN 20, 2020
A New MicroRNA Linked to the Suppression of Ovarian Cancer
One of the things a cancer patient can hear from their doctor is “recurrence.” Modern cancer therapies are a ...
Loading Comments...