Researchers discover a missing link in signals contributing to neurodegeneration

May 9, 2013

In many neurodegenerative diseases the neurons of the brain are over-stimulated and this leads to their destruction. After many failed attempts and much scepticism this process was finally shown last year to be a possible basis for treatment in some patients with stroke. But very few targets for drugs to block this process are known.

In a new highly detailed study, researchers have discovered a previously missing link between over-stimulation and destruction of , and shown that this might be a target for future drugs. This research, led by the A. I. Virtanen Institute at the University of Eastern Finland in collaboration with scientists from Lausanne University Hospital, University of Lausanne and the company Xigen Pharma AG, was published in the Journal of Neuroscience.

What is this missing link? We have known for years that over-stimulated neurons produce nitric oxide molecules. Although this can activate a signal for destruction of cells, the small amount of nitric oxide produced cannot alone explain the damage to the brain. The team now show that a protein called NOS1AP links the nitric oxide that is produced to the damage that results.. NOS1AP binds an initiator of called MKK3 and also moves within the cell to the source of nitric oxide when cells are over-activated.. The location of these proteins in cells causes them to convert the over-stimulation signal into a cell destruction response. The team designed a chemical that prevents NOS1AP from binding the source of nitric oxide. This reduces the cell destruction response in cells of the brain and as a result it limits in rodents.

This translational research was funded mainly by the Academy of Finland, the European Union and the University of Eastern Finland and used the recently developed high-throughput imaging facilities at the A. I. Virtanen Institute. The researchers hope that continuation of their work could lead to improved treatments for diseases such as stroke, epilepsy and chronic conditions like Alzheimer's disease. As NOS1AP is associated with schizophrenia, diabetes and sudden cardiac death, future research in this area may assist the treatment of a wider range of diseases.

Explore further: Discovery of nitric oxide delivery mechanism may point to new avenue for treating high blood pressure

More information: Li, L. et al. Anita C. Truttmann, and Michael J. Courtney. The nNOS-p38MAPK Pathway Is Mediated by NOS1AP during Neuronal Death, Journal of Neuroscience, 8 May 2013, 33(19):8185-8201; doi:10.1523/JNEUROSCI.4578-12.2013.

Related Stories

Bacteria producing nitric oxide extend life in roundworms

February 14, 2013

Nitric oxide, the versatile gas that helps increase blood flow, transmit nerve signals, and regulate immune function, appears to perform one more biological feat— prolonging the life of an organism and fortifying it against ...

A coordinated response to cardiac stress

March 1, 2013

Myocardial hypertrophy, a thickening of the heart muscle, is an adaptation that occurs with increased stress on the heart, such as high blood pressure. As the heart muscle expands, it also requires greater blood flow to maintain ...

Recommended for you

New insights on how cocaine changes the brain

November 25, 2015

The burst of energy and hyperactivity that comes with a cocaine high is a rather accurate reflection of what's going on in the brain of its users, finds a study published November 25 in Cell Reports. Through experiments conducted ...

Can physical exercise enhance long-term memory?

November 25, 2015

Exercise can enhance the development of new brain cells in the adult brain, a process called adult neurogenesis. These newborn brain cells play an important role in learning and memory. A new study has determined that mice ...

Umbilical cells help eye's neurons connect

November 24, 2015

Cells isolated from human umbilical cord tissue have been shown to produce molecules that help retinal neurons from the eyes of rats grow, connect and survive, according to Duke University researchers working with Janssen ...

Brain connections predict how well you can pay attention

November 24, 2015

During a 1959 television appearance, Jack Kerouac was asked how long it took him to write his novel On The Road. His response – three weeks – amazed the interviewer and ignited an enduring myth that the book was composed ...

No cable spaghetti in the brain

November 24, 2015

Our brain is a mysterious machine. Billions of nerve cells are connected such that they store information as efficiently as books are stored in a well-organized library. To this date, many details remain unclear, for instance ...


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.