Powerful molecules provide new findings about Huntington's disease

August 21, 2018, Lund University
Credit: CC0 Public Domain

Researchers at Lund University in Sweden have discovered a direct link between the protein aggregation in nerve cells that is typical for neurodegenerative diseases, and the regulation of gene expression in Huntington's disease. The results pave the way for the development of new treatment strategies for diseases that involve impairment of the basic mechanism by which the body's cells can break down and recycle their own component parts. This process, called autophagy, is disrupted in for example Huntington's and other neurodegenerative diseases.

The research, which is based on studies using cell culture and mouse models as well as human tissue from deceased individuals with Huntington's disease, is published in Cell Reports.

Like diseases such as Parkinson's and Alzheimer's, Huntington's is characterised by the accumulation of misfolded proteins, known as protein aggregates, in the brain's . The cells' function is impaired and signal pathways are lost. In Huntington's, an inherited and incurable neurodegenerative disease, this results in a combination of neurological, motoric, cognitive and psychiatric symptoms.

"We know very little about why arise or in what way they are involved in the development of the disease. However, our study shows that expression of the mutated Huntingtin gene impairs the nerve cells' ability to break down and recycle cellular material, which results in an accumulation of the protein AGO2", says Johan Jakobsson, researcher in molecular neurogenetics and leader of the study.

By activating the mechanism in the brain that breaks down and recycles material, known as , accumulation of the protein AGO2 could be blocked. As AGO2 is an important protein in the function of microRNAs, the researchers saw that changes in the autophagy mechanism also resulted in extensive changes in microRNA activity.

MicroRNA (miRNA) are very small, but powerful, molecules that have an important role in the regulation of genes, i.e. they have an influence on whether a certain gene is active or not – in this context how much of certain proteins is to be produced in the .

"Our study indicates that changes in miRNA levels are an early sign of Huntington's disease and are a result of changes in autophagy. It shows a direct link between aggregation and gene regulation", says Karolina Pircs, postdoc researcher in Johan Jakobsson's research team.

The researchers consider that the study provides support for the development of autophagy- activating therapies for Huntington's disease and other .

"If we can just find the right way to activate autophagy, we can perhaps effectively treat these diseases at an early stage. That is what we are currently working on in the lab", concludes Johan Jakobsson.

Explore further: Researchers discover system that could reduce neurodegeneration in Huntington's disease

More information: Karolina Pircs et al. Huntingtin Aggregation Impairs Autophagy, Leading to Argonaute-2 Accumulation and Global MicroRNA Dysregulation, Cell Reports (2018). DOI: 10.1016/j.celrep.2018.07.017

Related Stories

Researchers discover system that could reduce neurodegeneration in Huntington's disease

July 27, 2018
Neuroscientist Dr. David Vilchez and his team at CECAD, the University of Cologne's Cluster of Excellence for Aging Research, have made an important step toward understanding the mechanisms that cause the neurodegenerative ...

New insight into Huntington's disease may open door to drug development

July 9, 2018
McMaster University researchers have developed a new theory on Huntington's disease which is being welcomed for showing promise to open new avenues of drug development for the condition.

Strict eating schedule can lower Huntington disease protein in mice

March 6, 2018
New research from the University of British Columbia suggests that following a strict eating schedule can help clear away the protein responsible for Huntington disease in mice.

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

August 2, 2016
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.

Scientists develop therapeutic protein, protect nerve cells from Huntington's Disease

September 13, 2016
A new scientific study reveals one way to stop proteins from triggering an energy failure inside nerve cells during Huntington's disease. Huntington's disease is an inherited genetic disorder caused by mutations in the gene ...

New study uncovers how brain cells degrade dangerous protein aggregates

November 7, 2011
Researchers at the RIKEN Brain Science Institute (BSI) have discovered a key mechanism responsible for selectively degrading aggregates of ubiquitinated proteins from the cell. Their findings indicate that the capture and ...

Recommended for you

Mutation that causes autism and intellectual disability makes brain less flexible

November 19, 2018
About 1 percent of patients diagnosed with autism spectrum disorder and intellectual disability have a mutation in a gene called SETD5. Scientists have now discovered what happens on a molecular level when the gene is mutated ...

How the brain switches between different sets of rules

November 19, 2018
Cognitive flexibility—the brain's ability to switch between different rules or action plans depending on the context—is key to many of our everyday activities. For example, imagine you're driving on a highway at 65 miles ...

Signal peptides' novel role in glutamate receptor trafficking and neural synaptic activity

November 19, 2018
Glutamate is the major excitatory neurotransmitter in the brain, and the postsynaptic expression level of glutamate receptors is a critical factor in determining the efficiency of information transmission and the activity ...

Study explains behavioral reaction to painful experiences

November 19, 2018
Exposure to uncomfortable sensations elicits a wide range of appropriate and quick reactions, from reflexive withdrawal to more complex feelings and behaviors. To better understand the body's innate response to harmful activity, ...

Newborn babies' brain responses to being touched on the face measured for the first time

November 16, 2018
A newborn baby's brain responds to being touched on the face, according to new research co-led by UCL.

New brain imaging research shows that when we expect something to hurt it does, even if the stimulus isn't so painful

November 14, 2018
Expect a shot to hurt and it probably will, even if the needle poke isn't really so painful. Brace for a second shot and you'll likely flinch again, even though—second time around—you should know better.

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.