Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Cleaning up cellular trash

Inducing cells to destroy a misfolded protein alleviates the symptoms of Huntington's disease in mice

Huntington’s disease (HD) is a progressive neurodegenerative disease characterized primarily by involuntary movements. Inherited mutations in the huntingtin gene cause a stretch of glutamine residues in its associated protein, huntingtin, to increase in length, so that the mutant protein misfolds and accumulates within neurons. Neurologists believe that failure to clear aggregates of this misfolded protein is an underlying mechanism involved in the onset of HD.

Nerve cells can now be induced to destroy mutant huntingtin protein and reduce aggregate formation, according to the results of a study led by Nobuyuki Nukina of the RIKEN Brain Science Institute in Wako1. The researchers suggest that their approach could be used to effectively treat HD.

Nukina and colleagues used genetic engineering to construct a fusion protein consisting of two copies of polyglutamine binding peptide 1, which is known to bind mutant huntingtin and suppress its aggregation, and the binding regions of heat shock cognate protein 70 (HSC70), which is a ‘chaperone’ protein that targets the mutant huntingtin for destruction.

The researchers found that their construct inhibited the aggregation of mutant huntingtin in cultured cells by inducing a process called chaperone-mediated autophagy, which does not normally break down the misfolded proteins. They also observed that the fusion molecule bound to the mutant huntingtin, forming complexes with HSC70 that were recognized as abnormal and sent to a structure called the lysosome for degradation.

The construct was also effective in clearing aggregates of several other misfolded proteins, including ataxin1, which causes a neurodegenerative disease called spinocerebellar ataxia.

The researchers tested their construct in two strains of mice with HD symptoms. They injected viral vectors containing the construct into the striatum, a brain region that is involved in the control of movement and degenerates in HD patients.

When they examined the animals’ brains four weeks later, they found the construct widely distributed throughout the striatum in both mouse strains. Importantly, the fusion protein had significantly inhibited huntingtin aggregation compared to control mice. As well as reducing the number of aggregates, the construct reduced the average size of the remaining aggregates. The treatment also alleviated HD symptoms in the animals: their movements improved in a behavioral task, they lost less weight, and their survival rate increased.

“Genetic therapy for Huntington's is currently not possible because of the difficulties involved in delivering genes to the brain,” says Nukina, “so we would like to develop or find a compound that can bind to expanded glutamine tracts and HSC70.”

The corresponding author for this highlight is based at the Laboratory for Structural Neuropathology, RIKEN Brain Science Institute

Journal information

1. Bauer, P.O., Goswami, A., Wong, H.K., Okuno, M., Kurosawa, M., Yamada, M., Miyazaki, H., Matsumoto, G., Kino, Y., Nagai, Y. & Nukina, N. Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein. Nature Biotechnology 28, 256–263 (2010)

gro-pr | Research asia research news
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Novel mechanisms of action discovered for the skin cancer medication Imiquimod

21.10.2016 | Life Sciences

Second research flight into zero gravity

21.10.2016 | Life Sciences

How Does Friendly Fire Happen in the Pancreas?

21.10.2016 | Life Sciences

More VideoLinks >>>