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 Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>