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

Student develops microfluidics device to help scientists identify early genetic markers of cancer

October 16, 2018
As anyone who has played "Where's Waldo" knows, searching for a single item in a landscape filled with a mélange of characters and objects can be a challenge. Chrissy O'Keefe, a Ph.D. student in the Department of Biomedical ...

Researchers use brain cells in a dish to study genetic origins of schizophrenia

October 16, 2018
A study in Biological Psychiatry has established a new analytical method for investigating the complex genetic origins of mental illnesses using brain cells that are grown in a dish from human embryonic stem cells. Researchers ...

Why heart contractions are weaker in those with hypertrophic cardiomyopathy

October 16, 2018
When a young athlete suddenly dies of a heart attack, chances are high that they suffer from familial hypertrophic cardiomyopathy (HCM). Itis the most common genetic heart disease in the US and affects an estimated 1 in 500 ...

Importance of cell cycle and cellular senescence in the placenta discovered

October 15, 2018
Working with researchers from Stanford University and St. Anna Children's Cancer Research, researchers from Jürgen Pollheimer's laboratory at the Medical University of Vienna's Department of Obstetrics and Gynecology have ...

Team's study reveals hidden lives of medical biomarkers

October 12, 2018
What do medical biomarkers do on evenings and weekends, when they might be considered off the clock?

Researchers find a 'critical need' for whole genome sequencing of young cancer patients

October 12, 2018
St. Jude Children's Research Hospital has re-defined the gold standard for diagnostic testing of childhood cancer patients in the precision-medicine era and has implemented the testing for new cancer patients. The findings ...

0 comments

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.