Isoprenoids, Neuromelanin And Neuronal Vulnerability In Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$538,764.00
Summary
Parkinson's disease is a common and ultimately fatal brain disease which affects primarily normal movement. While a comparatively modest cell death occurs in other areas of the brain in Parkinson's disease, the motor symptoms result from the massive death of particular brain cells which are unique in that they contain a pigment called neuromelanin. This project aims to discover what makes the neuromelanin-containing cells of the brain particularly vulnerable to cell death in Parkinson's disease. ....Parkinson's disease is a common and ultimately fatal brain disease which affects primarily normal movement. While a comparatively modest cell death occurs in other areas of the brain in Parkinson's disease, the motor symptoms result from the massive death of particular brain cells which are unique in that they contain a pigment called neuromelanin. This project aims to discover what makes the neuromelanin-containing cells of the brain particularly vulnerable to cell death in Parkinson's disease. We recently found that neuromelanin pigment in the cells of people who have died with Parkinson's disease concentrate a fat-binding protein called alpha-synuclein which is thought to be important in causing cell death in Parkinson's disease. This association between the neuromelanin pigment and alpha-synuclein was not found in other cells in Parkinson brain which do not contain pigment, nor in the brains of healthy people. We also found that a third of neuromelanin is made up of a special group of fats called isoprenoids. Changes in these fats have already been reported in the blood in Parkinson's disease. We suggest that specific changes in the isoprenoid fats in neuromelanin in Parkinson's disease cause alpha-synuclein protein to accumulate on the fat in the pigment, as well as other cellular changes which are detrimental to the cell, ultimately leading to the death of the cell. These changes may explain for the first time why neuromelanin-containing brain cells are especially vulnerable in Parkinson's disease and provide new avenues for treating this disorder.Read moreRead less
In Parkinson's disease only specific brain cells die, these cells are unusual in that they contain a dark coloured pigment called neuromelanin. The presence of this pigment is thought to play a role in the death of these cells. Evidence from many different diseases has demonstrated that a type of cell damage called oxidative damage is caused by an increase in tissue iron levels. Iron levels are increased in the brains of persons who have died with Parkinson's disease but only in the part of the ....In Parkinson's disease only specific brain cells die, these cells are unusual in that they contain a dark coloured pigment called neuromelanin. The presence of this pigment is thought to play a role in the death of these cells. Evidence from many different diseases has demonstrated that a type of cell damage called oxidative damage is caused by an increase in tissue iron levels. Iron levels are increased in the brains of persons who have died with Parkinson's disease but only in the part of the brain which contains neuromelanin. This increase in iron is thought to lead to oxidative damage and thus cell death in Parkinson's disease. Why iron should be increased specifically in this part of the brain is unknown but it has been shown that neuromelanin binds tissue iron and that the interaction between iron and neuromelanin can result in tissue damage. These events are suggested to underlie the specific vulnerability of the neuromelanin-containing cells in Parkinson's disease. However as yet very little is known about this pigment or how it interacts with iron. This research investigates neuromelanin in the normal brain and in the brain of persons who have died with Parkinson's disease. The project aims to demonstrate how neuromelanin interacts with iron and how neuromelanin, both in the presence and absence of iron, can influence oxidative cell damage. The use of human neuromelanin makes this research unique and it will provide important and novel information regarding the role of this pigment in the aetiology of this devastating disease.Read moreRead less