Amyotrophic Lateral Sclerosis (ALS), also known as Motor Neurone Disease, Lou Gehrig’s Disease, or Maladie de Charcot affects from one to five out of every 100,000 people. It is a fatal, progressive neurodegenerative disease caused by the degeneration of motor neurons in the central nervous system which control voluntary muscle movement.
Researchers at the University of Bath have found a causal link between the gene which produces angiogenin - a protein involved in blood vessel formation- and the development of some forms of ALS.
Some famous people afflicted with the disease are actor David Niven, athletes Don Revie and Willie Maddren, and baseball player Lou Gehrig. Professor Stephen Hawking is a notable anomaly, since has survived with the disease for over 35 years.
From the press release:
“In a series of recent papers, including the latest one in HMG, Dr Vasanta Subramanian and colleagues from the University of Bath have shown that as well as playing a key role in the formation of blood vessels, angiogenin is also involved in maintaining motor neurones. The scientists behind the new research believe that the gradual build up of these faulty molecules may explain the late onset and gradual deterioration of function caused by the disease.
By targeting the altered form of angiogenin, it may be possible to better maintain the neurones of people with the disease, in order to prevent them from degenerating and halt progression of the disease."
Researchers sought out sites where angiogenin is produced in developing embryos of mice, and found that it was extensively produced in the nervous system, both in the brain and in the spinal cord, chiefly in the neurons. Levels of angiogenin gradually fell as the mouse embryo developed, but was still seen in brains and spinal cords of adult mice.
A molecule was then used to suppress the activity of the angiogenin gene in neurons. The absence of angiogenin affected the neurones ability to extend nerve projections; a process called neurite pathfinding. Effects of a mutated angiogenin on motor neurones were then examined and it was found that the molecule effects motor neurone pathfinding.
It was also discovered that the mutated angiogenin is toxic to motor neurones when the nerve cells are subjected to oxidative stress. It can be concluded from these findings that angiogenin acts as a neurotrophic and neuroprotective factor that helps neurones to survive.
Mutated Angiogenin Mystery
“We know most about angiogenin from its role in helping blood vessels branch into the tree-like structures as they grow, particularly in tumour growth,"
said Dr Vasanta Subramanian from the University of Baths Department of Biology & Biochemistry.
“Last years discovery that some patients with both familial and sporadic Motor Neurone Disease have a mutated version of the human angiogenin gene was surprising because we didnt know how angiogenin could be connected with the disease. Since then we have been busy trying to find out, and now we have shown that angiogenin also plays a key role in the maintenance and development of motor neurones.
We have also found that mutated versions of this molecule are toxic to motor neurones and affect their ability to put out extensions called the axons. This clearer picture of how the altered angiogenin works at the cellular and molecular level enables us to think about ways of preventing the disease from progressing."
“The symptoms of Motor Neurone Disease begin to appear as the neurones which control movement begin to degenerate. If we can block the function of the faulty angiogenin in patients in which it is present this may help to maintain healthy neurones and prevent further progression of the disease.”
- For a video presentation of an interview with Dr Subramanian click here
Image: Jose-Luis Olivares/MIT