Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular Mechanism responsible for a neurodegenerative disease discovered

07.01.2016

Scientists from Bern have discovered a mechanism which is responsible for the degeneration of Purkinje cells in the cerebellum in a neurodegenerative disease called Spinocerebellar ataxia type 1. The results of their study open up new avenues for the future treatment of cerebellum associated degenerative disorders.

Damage, degeneration or loss of neurons in the region of the brain that controls muscle coordination (cerebellum), results in ataxia. The symptoms include loss of voluntary coordination of muscle movements and the appearance of gait abnormality, loss of balance and speech problems.


Left: A healthy Purkinje cell displaying an elaborate dendritic arbor covered in spines. Right: A Purkinje cell afflicted with ataxia, showing classical hallmarks of degeneration

Institute of Cell Biology, University of Bern

Cerebellar ataxias are progressive degenerative disorders which occur in adults either sporadically or can be inherited from parents. Unfortunately, the large majority of cerebellar ataxia cases are sporadic in nature and the causative mechanism for the development of ataxia remains largely unknown, which eventually hinders the development of therapy and negatively influences the quality of patient’s life.

However, both the sporadic and inherited cases of cerebellar ataxia exhibit common pathophysiological characteristics such as the specific degeneration of the main cerebellar neurons; the Purkinje cells. Therefore, the team of Smita Saxena from the Institute of Cell Biology at the University of Bern set out to understand the potential mechanism involved in the development of ataxia and degeneration of Purkinje cells in Spinocerebellar ataxia type 1 (SCA1), a rare, incurable, inheritable neurodegenerative disease that can be modeled in mice.

Together with first author Céline Ruegsegger, a protein based screening of Purkinje cells was performed to identify changes that occur in these neurons at the time of ataxia appearance. The team discovered wide spread alterations in proteins which function at the synapse and identified a synaptic protein Homer-3 that is mainly present in Purkinje cell synapses to be reduced.

Further, they found that Homer-3 decrease was related to the alteration in an important signaling pathway; mTORC1. This signaling pathway was responsible for regulating the expression of synaptic proteins such as Homer-3. Saxena and her team have discovered a cellular mechanism in the cerebellum of SCA1 mice that specifically targets the degeneration of Purkinje cells and the findings present a promising future therapeutic target. The study was published in the scientific journal «Neuron».

The team investigated why mTORC1 signaling was altered in the cerebellar Purkinje cells and not in other regions of the brain. By measuring activation state of Purkinje cells, they found that impaired mTORC1 signaling was due to defects in Purkinje cell associated neuronal circuitry mainly involving the climbing fibers.

“In this context, the identification of circuit related alterations which play an important role in determining pathological alterations in Purkinje cells is important in understanding how the disease mechanism works and targets vulnerable components in defined neurons; in this case Purkinje cells,” says Saxena.

Reinstating Homer-3 expression can ameliorate symptoms and delay pathology
After the identification of Homer-3 as being reduced early in the disease course, Céline Ruegsegger and Saxena tried to establish its causal role in the development of disease. By using a gene therapy approach they reintroduced Homer-3 expression in Purkinje cells of SCA1 mice. This slowed down the development of ataxia, ameliorated symptoms associated with loss of motor coordination and balance and restored Purkinje cell functionality.

“Interestingly, it has been known for some time that alterations in mTORC1 signaling in the cerebellum during development is associated with autistic behavior and intellectual disorder,” said Saxena. “In our study, the novel finding is that similar signaling pathways can also be involved in adult cerebellar associated degenerative disorders such as SCA1. This is an important step forward in understanding the process involved in developmental and degenerative disorders and identifies a potentially new therapeutic target for the future.”

Publication details:
Céline Ruegsegger, David M. Stucki, Silvio Steiner, Nico Angliker, Julika Radecke, Eva Keller, Benoît Zuber, Markus A. Rüegg and Smita Saxena
Impaired mTORC1-dependent expression of Homer-3 influences SCA1 pathophysiology. Neuron, 2016 (in press)

Weitere Informationen:

http://www.unibe.ch/news/media_news/media_relations_e/media_releases/2016_e/inde...

Nathalie Matter | Universität Bern

More articles from Life Sciences:

nachricht Switch-in-a-cell electrifies life
18.12.2018 | Rice University

nachricht Plant biologists identify mechanism behind transition from insect to wind pollination
18.12.2018 | University of Toronto

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Data storage using individual molecules

Researchers from the University of Basel have reported a new method that allows the physical state of just a few atoms or molecules within a network to be controlled. It is based on the spontaneous self-organization of molecules into extensive networks with pores about one nanometer in size. In the journal ‘small’, the physicists reported on their investigations, which could be of particular importance for the development of new storage devices.

Around the world, researchers are attempting to shrink data storage devices to achieve as large a storage capacity in as small a space as possible. In almost...

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Pressure tuned magnetism paves the way for novel electronic devices

18.12.2018 | Materials Sciences

New type of low-energy nanolaser that shines in all directions

18.12.2018 | Physics and Astronomy

NASA research reveals Saturn is losing its rings at 'worst-case-scenario' rate

18.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>