Final Report Summary - NEURONE (Molecular mechanisms of neuronal degeneration: from cell biology to the clinic)
Over the past year NEURONE researchers have shown that much of the toxicity that kills motoneurons comes from the surrounding tissue rather than the cells themselves or the muscles that they connect to. Various inflammation-related changes have been found. Within the motoneurons damage to the nerve fibres is one of the first events, particularly through failure of the transport systems that take material to the ends of the nerve fibres. New mechanisms that lead to this damage have been discovered, together with a decrease in a calcium-related molecule that makes the motoneurons more vulnerable.
Huntington's disease is a genetic conditions that causes degeneration of neurons, usually starting in middle age. It is due to the attachment of excess DNA coding for polyglutamine repeats to the huntingtin protein. NEURONE researchers have found two ways in which this mutation can lead to neuronal death. One discovery is that the mitochondria become very vulnerable to toxic insults, particularly those involving calcium. The second discovery is that production of a key growth factor, BDNF, and its receptor are affected in the Huntington brain.
For Parkinson's disease patients transplantation of immature dopaminergic neurons has provided a partial cure. Recent NEURONE research has shown that in patients who had these transplants almost 20 years ago, the implanted cells are developing signs of Parkinson's disease. This is an important finding because it shows that the environment surrounding the affected neurons is a key factor in the cause of the condition. NEURONE researchers are developing better forms of transplant by selecting the optimal cell type and by producing them from stem cells.
One of the pharma companies associated with NEURONE has developed compounds that localise to the membranes of neurons, and bind excess metal ions. This can prevent various toxic events in the cell, which depend on the activation of enzymes by these metal ions. Recent work has shown that these compounds are successful at slowing the development of Alzheimer's disease in animal models. Treated animals show improved cognitive skills and less pathology in the brain.
Plasticity is the process that allows the damaged brain to compensate for damage by producing new circuits. In adults plasticity is much lower than in children, which means that adults have a limited ability to recover after brain or spinal cord damage. An enzyme called chondroitinase has been found to reactivate plasticity in the adult brain and spinal cord. This treatment alone produces some functional recovery after spinal cord injury. In the past year NEURONE researchers have found that combining rehabilitation treatment with chondroitinase in order to drive the plastic changes produces a greatly increased degree of functional recovery.
NEURONE has developed a set of activities suitable for demonstrations in science museums and open days. Visitors can experience three methods that are used to assess brain function in patients with Alzheimer's, Parkinson's and Huntington's disease. They perform computer-generated cognitive tests, tests of eye movement control and a test of the ability for rapid movement. This programme was taken to the science museums in London and Madrid.
NEURONE has created a DVD to present the life of people affected by neurodegenerative diseases and to explain how networks of excellence, such as NEURONE, can develop new therapeutic solutions for these patients.
Huntington's disease is a genetic conditions that causes degeneration of neurons, usually starting in middle age. It is due to the attachment of excess DNA coding for polyglutamine repeats to the huntingtin protein. NEURONE researchers have found two ways in which this mutation can lead to neuronal death. One discovery is that the mitochondria become very vulnerable to toxic insults, particularly those involving calcium. The second discovery is that production of a key growth factor, BDNF, and its receptor are affected in the Huntington brain.
For Parkinson's disease patients transplantation of immature dopaminergic neurons has provided a partial cure. Recent NEURONE research has shown that in patients who had these transplants almost 20 years ago, the implanted cells are developing signs of Parkinson's disease. This is an important finding because it shows that the environment surrounding the affected neurons is a key factor in the cause of the condition. NEURONE researchers are developing better forms of transplant by selecting the optimal cell type and by producing them from stem cells.
One of the pharma companies associated with NEURONE has developed compounds that localise to the membranes of neurons, and bind excess metal ions. This can prevent various toxic events in the cell, which depend on the activation of enzymes by these metal ions. Recent work has shown that these compounds are successful at slowing the development of Alzheimer's disease in animal models. Treated animals show improved cognitive skills and less pathology in the brain.
Plasticity is the process that allows the damaged brain to compensate for damage by producing new circuits. In adults plasticity is much lower than in children, which means that adults have a limited ability to recover after brain or spinal cord damage. An enzyme called chondroitinase has been found to reactivate plasticity in the adult brain and spinal cord. This treatment alone produces some functional recovery after spinal cord injury. In the past year NEURONE researchers have found that combining rehabilitation treatment with chondroitinase in order to drive the plastic changes produces a greatly increased degree of functional recovery.
NEURONE has developed a set of activities suitable for demonstrations in science museums and open days. Visitors can experience three methods that are used to assess brain function in patients with Alzheimer's, Parkinson's and Huntington's disease. They perform computer-generated cognitive tests, tests of eye movement control and a test of the ability for rapid movement. This programme was taken to the science museums in London and Madrid.
NEURONE has created a DVD to present the life of people affected by neurodegenerative diseases and to explain how networks of excellence, such as NEURONE, can develop new therapeutic solutions for these patients.
