Researchers identify how a single gene can protect against causes of neurodegenerative diseases

August 2, 2016, University of Glasgow
Researchers identify how a single gene can protect against causes of neurodegenerative diseases
Credit: University of Glasgow

New research has identified how cells protect themselves against 'protein clumps' known to be the cause of neurodegenerative diseases including Alzheimer's, Parkinson's and Huntington's disease.

The study, which is published today in Cell and was conducted by the University of Glasgow in collaboration with the MRC Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee, offers an insight into the role of a gene called UBQLN2 and how it helps to remove toxic protein clumps from the body and protect it from disease.

Using biochemistry, cell biology and sophisticated mouse models, the researchers discovered that the main function of UBQLN2 is to help the cell to remove dangerous protein clumps – a role which it performs by first detangling clumps, then shredding them to prevent future tangles.

Protein clumps occur as part of the , but are normally detangled and disposed of as a result of the gene UBQLN2. However when this gene mutates, or becomes faulty, it can no longer help the cell to remove these toxic protein clumps, which leads to neurodegenerative disease.

Dr Thimo Kurz, from the Institute of Molecular, Cell and Systems Biology, said: "The function of UBQNL2 is connected to many neurodegenerative disorders, such as Parkinson's, Alzheimer's and Huntington's disease.

"These patients often have very clear clumps in their brain cells. Using mice that mimic human Huntington's disease, we found that when UBQLN2 is mutated, it could no longer help nerve to remove protein clumps in the brains of these mice."

Previous work has shown that when the UBQLN2 gene is faulty, it leads to a neurodegenerative disease called Amyotrophic Lateral Sclerosis with Frontotemporal Dementia (ALS/FTD or motor-neuron disease with dementia). However until this study it was not fully understood why mutation of this gene caused disease.

Now that scientists understand exactly how UBQLN2 works and what it does, they are also able to understand why its mutation appears to be so detrimental to the body.

Indeed they hope that their findings will pave the way for new research into novel treatment options for patients with .

Dr Roland Hjerpe said: "The significance of this discovery goes beyond the role of UBQLN2 in motor-neuron disease with dementia.

"Our study has revealed a new mechanism by which cope with protein clumps in general, which has implications for most neurodegenerative diseases and can open up avenues for new therapeutic interventions to treat these conditions in the future."

Explore further: New insight into the most common genetic cause of ALS and FTD

More information: Roland Hjerpe et al. UBQLN2 Mediates Autophagy-Independent Protein Aggregate Clearance by the Proteasome, Cell (2016). DOI: 10.1016/j.cell.2016.07.001

Related Stories

New insight into the most common genetic cause of ALS and FTD

June 30, 2016
Scientists from the University of Sheffield have discovered a novel function of the C9orf72 protein which is linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) - giving a new insight into the ...

New areas of the brain identified where ALS-implicated gene is active

August 1, 2016
For the first time novel expression sites in the brain have been identified for a gene which is associated with motor neuron disease and frontotemporal dementia.

Structure of brain plaques in Huntington's disease described

February 3, 2016
Researchers at the University of Pittsburgh School of Medicine have shown that the core of the protein clumps found in the brains of people with Huntington's disease have a distinctive structure, a finding that could shed ...

Designer protein gives new hope to scientists studying Alzheimer's disease

July 22, 2016
A new protein which will help scientists to understand why nerve cells die in people with Alzheimer's disease has been designed in a University of Sussex laboratory.

More evidence in quest to repurpose cancer drugs for Alzheimer's disease

July 27, 2016
An FDA approved drug to treat renal cell carcinoma appears to reduce levels of a toxic brain protein linked to dementia in Alzheimer's and Parkinson's diseases when given to animals. This finding is the latest from Georgetown ...

New study opens new door for ALS drug discovery

December 28, 2015
To create treatments for a disease without any, scientists need to study and understand the driving forces behind the faulty biology. Today, researchers at the University of North Carolina School of Medicine announced the ...

Recommended for you

Once-mysterious 'Atacama Skeleton' illuminates genetics of bone disease

March 22, 2018
The skeleton, discovered in a leather pouch behind an abandoned church, was pristine: a tiny figure, just six inches long, with a cone-shaped head, 10 pairs of ribs, and bones that looked like those of an eight-year-old child. ...

Early life experiences influence DNA in the adult brain

March 22, 2018
In the perennial question of nature versus nurture, a new study suggests an intriguing connection between the two. Salk Institute scientists report in the journal Science that the type of mothering a female mouse provides ...

Study reveals startlingly different tissue sensitivities to cancer-driving genes

March 22, 2018
New research led by Harvard Medical School and Brigham and Women's Hospital has unmasked hundreds of cancer-driving genes and revealed that different tissue types have shockingly variable sensitivities to those genes.

Does genome sequencing increase downstream costs?

March 22, 2018
As genome sequencing enters the clinic, fears have arisen about its potential to motivate follow-up testing and ongoing screening that could drastically increase health care spending. But few studies have quantified the downstream ...

First 'non-gene' mutations behind neurodevelopmental disorders discovered

March 21, 2018
In the largest study of its kind, genetic changes causing neurodevelopmental disorders have been discovered by scientists at the Wellcome Sanger Institute and their collaborators in the NHS Regional Genetics services. The ...

Two genes likely play key role in extreme nausea and vomiting during pregnancy

March 21, 2018
Most women experience some morning sickness during pregnancy, but about 2 percent of pregnant women experience a more severe form of nausea and vomiting.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.