How mutations lead to neurodegenerative disease

May 13, 2019

Scientists have discovered how mutations in DNA can cause neurodegenerative disease. The discovery is an important step towards better treatment to slow the progression or delay onset in a range of incurable diseases such as Huntington's and motor neurone disease - possibly through the use, in new ways, of existing anti-inflammatory drugs.

The team of scientists has shown experimentally, for the first time, how mutations ultimately set off an anti-viral like inflammatory response in cells that leads to cell death and, over time, progressive neurological damage.

Led by the University of Adelaide, the study published in Human Molecular Genetics is the culmination of over a decade of research with researchers at the Victor Chang Research Institute in Sydney, seeking to understand how DNA mutations result in neurological damage.

This study investigates the outcomes of a mutation linked to Huntington's disease and 20 other neurodegenerative diseases, including some forms of motor neurone disease. But it also may have implications for the progression of neurodegenerative diseases which aren't necessarily inherited, such as Alzheimer's and Parkinson's, which evidence suggests are caused by a similar inflammatory response to environmental triggers.

"Together these conditions affect millions of families worldwide, and there are no cures or effective treatments," says project leader Rob Richards, Professor of Genetics in the University of Adelaide's School of Biological Sciences.

"If the new mechanism we have discovered proves to be correct, it will transform the field, providing a different way of thinking about these diseases and offering new opportunities for medical intervention."

The so-called 'DNA repeat diseases' - named because of the repeat sequences found in the DNA of patients - share many common features in their symptoms, but the mechanisms by which symptoms arise have previously been thought to be different for each.

"We've known what mutations are involved for some years, and the set of outcomes that result, but, until now, we've not known how one leads to the other. This new research shows us how each of these diseases can be caused by the same underlying cellular pathway."

The study results centre around RNA, the molecule in our cells which is the intermediate step between the DNA in chromosomes and the proteins that are the cells' main functional components.

The DNA provides a blueprint for producing RNA that is then normally 'bar-coded' to ensure cells recognise it as "self", distinguishing it from the RNA of a foreign invader, such as viruses. Using the experimental model fly Drosophila, Professor Richards and his team showed that the affected, 'double-stranded RNA' was instead recognised as foreign to the body, or "non-self".

"This elicits an anti-viral like, auto-inflammatory response that leads to neuronal destruction and death, in time causing progressive neurological damage," says Professor Richards. "The abnormal RNA is made from regions of repeated DNA sequences that are found in greater numbers in people affected with Huntington's and some other neurodegenerative diseases."

Professor Richards says there are existing drugs for other types of auto-inflammatory disease, which may prove to be effective in treating the symptoms of these diseases, by inhibiting the anti-viral inflammatory response.
-end-
Media Contact:

Professor Rob Richards, School of Biological Sciences, The University of Adelaide. Mobile: +61 (0)422 007 867, robert.richards@adelaide.edu.au

Robyn Mills, Media Officer, University of Adelaide. Phone: +61 (0)8 8313 6341, Mobile: +61 (0)410 689 084, robyn.mills@adelaide.edu.au

University of Adelaide

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA 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.