The Role Of Lycopene Supplementation In The Management Of Asthma
Funder
National Health and Medical Research Council
Funding Amount
$332,875.00
Summary
Asthma is a significant and increasing health problem for Australia and is now listed as a National Health Priority Area. There is immense community interest in dietary factors affecting asthma. This project examines the potential for dietary carotenoids to be used to manage asthma. Carotenoids are antioxidants that are found in orange and red fruits and vegetables, such as tomatoes, carrots and mangoes. Research suggests that dietary carotenoids may be protective against asthma symptoms and -or ....Asthma is a significant and increasing health problem for Australia and is now listed as a National Health Priority Area. There is immense community interest in dietary factors affecting asthma. This project examines the potential for dietary carotenoids to be used to manage asthma. Carotenoids are antioxidants that are found in orange and red fruits and vegetables, such as tomatoes, carrots and mangoes. Research suggests that dietary carotenoids may be protective against asthma symptoms and -or onset. It is also likely that increasing intake of carotenoid-rich foods may be more effective than taking dietary supplements, as the key nutrients or combination of nutrients may not be known. This project will examine whether carotenoids such as lycopene can reduce the tendency of asthmatic airways to overreact to common triggers. It also investigates whether carotenoids can be used to prevent or reduce the severity of asthma attacks. The project will determine whether tomato juice or lycopene capsules are more effective in this role. This work will provide the necessary information to develop a large trial testing the ability of carotenoids to improve quality of life for people with asthma. While there is evidence to suggest that carotenoids may be helpful in asthma, the data to date is inconclusive. This study provides a scientific approach to evaluating the potential for carotenoids to be used as a treatment for asthma.Read moreRead less
Gamma-Tocopherol: An Important Dietary Factor For Protection Against Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$341,575.00
Summary
Heart disease is one of the most common causes of death in Western Countries. Oxidative damage is thought to be a major contributor to the development of a number of chronic diseases such as heart disease. Oxidative damage can occur in states of oxidative stress when the body's antioxidant defences cannot prevent damage caused by free radicals or other oxidants. Antioxidant vitamins help defend against oxidative injury and therefore should help to protect against such diseases as heart disease ( ....Heart disease is one of the most common causes of death in Western Countries. Oxidative damage is thought to be a major contributor to the development of a number of chronic diseases such as heart disease. Oxidative damage can occur in states of oxidative stress when the body's antioxidant defences cannot prevent damage caused by free radicals or other oxidants. Antioxidant vitamins help defend against oxidative injury and therefore should help to protect against such diseases as heart disease (atherosclerosis). Population studies support the view that dietary antioxidants such as vitamin E help to protect against heart disease. However, several large studies giving subjects vitamin E supplements (pure alpha tocopherol) showed no benefits or protection against heart disease. There is a cruicial difference between supplements and dietary intake of vitamin E. Supplements contain only alpha tocopherol while dietary sources derived from seeds, nuts, grain and oils is a mixture of different forms of tocopherol. Recent evidence suggests that one of these forms (gamma-tocopherol) has different properties to alpha-tocopherol and can protect against certain oxidants in ways that alpha-tocopherol cannot. We have developed a specialised assay to detect forms of gamma-tocopherol in human plasma that have reacted with toxic oxidants. Using this assay we have shown that people with heart desease may have higher levels of these products in their blood than people without heart disease. This project will investigate the effects of gamma and alpha tocopherol dietary supplements on risk factors for heart disease. It will also investigate how gamma tocopherol may be working to protect against the development of heart disease. These studies could have important implications for what type of diet or dietary supplement is most beneficial to protect against heart disease.Read moreRead less
NOX Isoforms In Diabetes Associated Vascular Injury: Implications For Therapeutic Strategies
Funder
National Health and Medical Research Council
Funding Amount
$441,511.00
Summary
These studies will investigate the role of oxidative stress and enzymes involved in oxidative stress production in diabetes associated blood vessel injury and kidney damage, leading to heart attacks, stroke and kidney failure. We will use unique knockout animal models and novel drug treatments. Ultimately, we aim to develop novel treatments to better treat and prevent diabetes related complications.
Investigation Of The Role Of The ATM Protein In Peroxisome Function And Biogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$250,756.00
Summary
Ataxia-telangiectasia (A-T) is a complex multisystem disease characterized by extreme sensitivity to ionizing radiation (X-rays) and susceptibility to cancer, however the most debilitating symptoms are neurodegeneration and susceptibility to bronchial infections. The gene (atm) which is mutated in this disease has recently been cloned and current research is focussed on the function of the protein (termed ATM) that this gene encodes. We have localized the ATM protein to the nucleus, where it pla ....Ataxia-telangiectasia (A-T) is a complex multisystem disease characterized by extreme sensitivity to ionizing radiation (X-rays) and susceptibility to cancer, however the most debilitating symptoms are neurodegeneration and susceptibility to bronchial infections. The gene (atm) which is mutated in this disease has recently been cloned and current research is focussed on the function of the protein (termed ATM) that this gene encodes. We have localized the ATM protein to the nucleus, where it plays a role in monitoring DNA damage, and also to vesicles in the cytoplasm of the cell. We have demonstrated that some of these vesicles are peroxisomes, vital cellular organelles involved in a wide range of metabolic functions. The importance of peroxisomes is evidenced by the severe abnormalities in patients with disorders of peroxisome formation and function. Interestingly many of the neurological features of these patients overlap with those displayed by A-T patients. We propose that abnormalities in peroxisomal function in A-T may contribute to the development of neurological symptoms and we plan to examine the function of peroxisomes in cells from A-T patients, and in tissues from A-T mutant mice. This work may help design new treatments to ameliorate the most debilitating aspects of this disease.Read moreRead less
MITOCHONDRIA, OXIDATIVE STRESS AND NEURONAL APOPTOSIS: BIOCHEMICAL, CELLULAR AND PHARMACOLOGICAL APPROACHES
Funder
National Health and Medical Research Council
Funding Amount
$145,880.00
Summary
Our goal is to understand the detailed process whereby nerve cells die after various stresses and injury. We aim also to develop novel ways of protecting cells against such death. The death of nerve cells plays an important role in a series of neurodegenerative diseases, such as Parkinson's, Huntington's and Motor Neurone Diseases. One prevalent cause of cell death arises from the action of transmitters that normally signal between nerve cells but which, under conditions of stress and injury, ca ....Our goal is to understand the detailed process whereby nerve cells die after various stresses and injury. We aim also to develop novel ways of protecting cells against such death. The death of nerve cells plays an important role in a series of neurodegenerative diseases, such as Parkinson's, Huntington's and Motor Neurone Diseases. One prevalent cause of cell death arises from the action of transmitters that normally signal between nerve cells but which, under conditions of stress and injury, cause overstimulation of the nerve cells leading to death (excitotoxicity). Mitochondria are component of cells normally providing energy for the cell to carry out its various functions; but under stress conditions mitochondria act as controllers in cellular decision-making processes leading to cell death. Moreover, mitochondria are known to play an important role in neurodegenerative diseases, as they are a source of damaging oxygen derivatives called free radicals that cause cell injury. Mitochondria are also involved in death resulting from excitotoxicity. In order to understand the detailed mechanism of the nerve cell death process, we will use cultured nerve cells from the brains of laboratory mice, including both normal mice and those that are models of neurodegenerative disease. Injury leading to death will be induced by analogues of the transmitters that cause excitotoxicity. We will concentrate the those aspects of the death process that involve mitochondria, as this will enable us to test a range of antioxidants that can be expected to lead to new drug treatments for neuronal cell injury. Included in these compounds are novel antioxidants that are targeted to mitochondria. This project brings together the expertise in neuroscience and pharmacology of Professor Beart with the skills in biochemistry of Professor Nagley, particularly in mitochondrial and cell death research, to address this important medical research problem in a multidisciplinary manner.Read moreRead less
Mechanisms Of Cell Death In Focal Cerebral Ischaemia
Funder
National Health and Medical Research Council
Funding Amount
$229,624.00
Summary
Stroke most commonly results from interruption to a major artery in the brain. If not rapidly reversed the reduction in blood flow leads to the death of many cells in the brain tissue. There is currently considerable interest in developing treatments to be used in the early stages of stroke that can reduce cell death. As the extent of cell death is the major determinant of the long-term disabilities from stroke, such treatments are likely to provide considerable benenfits for affected individual ....Stroke most commonly results from interruption to a major artery in the brain. If not rapidly reversed the reduction in blood flow leads to the death of many cells in the brain tissue. There is currently considerable interest in developing treatments to be used in the early stages of stroke that can reduce cell death. As the extent of cell death is the major determinant of the long-term disabilities from stroke, such treatments are likely to provide considerable benenfits for affected individuals. Our study will investigate mechanisms underlying the death of brain cells in an animal model of stroke and in cells treated in culture. These studies will specifically focus on the role in cell death of alterations in mitochondria, a part of the cell that provides the energy needed for their normal function. The proposed investigations will identify molecular events that contribute to the mitochondrial dysfunction and examine the importance of these changes in brain tissue damage. The findings should contribute to the identication of new therapeutic approaches aimed at ameliorating the consequences of stroke.Read moreRead less
The Efficacy Of N-acetylcysteine As An Adjunctive Treatment In Unipolar Depression
Funder
National Health and Medical Research Council
Funding Amount
$443,832.00
Summary
This is evidence that the brain's antioxidant defences, particularly glutathione, are altered in depression. N-acetylcysteine (NAC), a glutathione precursor, increases antioxidant defences and has antidepressant properties in bipolar disorder. The aim of this study is to see if treatment with NAC will precent relapse and improve the symptoms of depression including functioning and quality of life. Participants will be randomly given either NAC or placebo, in addition to standard thereapy.
Mitochondrial L-arginine Transport And Its Role In The Pathogenesis Of Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$525,660.00
Summary
Heart failure is a common disorder that is marked by significant symptoms and reduced survival. Reduced cardiac performance is the key responsible mechanism. At the tissue level, altered energy metabolism is a major contributor. Mitochondria are the cellular elements that produce energy and in this project we aim to study how a key process that regulates mitochondrial activity behaves in the setting of heart failure.
Characterisation Of Antioxidant Pathways Involving Gpx-1: Implications For Neural Ischemic Reperfusion Injury.
Funder
National Health and Medical Research Council
Funding Amount
$458,250.00
Summary
Neural damage following stroke can be grouped into two stages. The first occurs immediately following the ischemic insult and results in the rapid loss of neural cell viability; the second stage (which usually results in severe neural dysfunction) occurs over many hours following reperfusion. There is however, a window of opportunity shortly following the ischemia-reperfusion where damage to the brain can be minimized if appropriate therapeutic intervention was available. However, our ability to ....Neural damage following stroke can be grouped into two stages. The first occurs immediately following the ischemic insult and results in the rapid loss of neural cell viability; the second stage (which usually results in severe neural dysfunction) occurs over many hours following reperfusion. There is however, a window of opportunity shortly following the ischemia-reperfusion where damage to the brain can be minimized if appropriate therapeutic intervention was available. However, our ability to identify novel targets and devise strategies for the treatment of stroke relies on our understanding of (a) the molecular processes that are initiated following brain ischemia and (b) the delayed molecular events that follow reperfusion and hypoperfusion and result in extensive neuronal loss. A major component that accompanies stroke is the generation of oxidative stress. Reactive oxygen species (ROS) are thought to make a significant contribution to neuronal cell injury and death during both the early and late stages following ischemia. Therefore the molecular pathways that are involved in ROS generation are prime targets for the development of improved therapies. It has already been established by us that the antioxidant enzyme, glutathione peroxidase-1 (Gpx-1) is essential in protecting neurons from ischemic injury-death. A clearer understanding of how Gpx-1 confers this protection in vivo would make an important contribution towards the design of improved treatments. In this proposal, we plan to determine the role of Gpx-1 in an in vivo model of stroke to: (1) demonstrate in a broader sense the functional importance of this antioxidant enzyme in neuronal survival and (2) to demonstrate in a more specific manner, the impact of this enzyme on two signaling molecules, PI3kinase (PI3K) and NFkB (both of which are redox sensitive and play important roles in neuronal cell viability) and their relevance to ischemic cell injury and death.Read moreRead less
Parkinson's Disease (PD) is one of the most common neurodegenerative disorders. Its incidence increases steadily with age affecting approximately 1% of the population at age 65 and up to 5% by the age of 85. At the time of diagnosis, patients suffer from a range of motor impairments that worsen over time. Pathologically these patients are characterised by the accumulation of a protein known as alpha-synuclein in specific types of nerve cells in their brain. However, the function of this protein ....Parkinson's Disease (PD) is one of the most common neurodegenerative disorders. Its incidence increases steadily with age affecting approximately 1% of the population at age 65 and up to 5% by the age of 85. At the time of diagnosis, patients suffer from a range of motor impairments that worsen over time. Pathologically these patients are characterised by the accumulation of a protein known as alpha-synuclein in specific types of nerve cells in their brain. However, the function of this protein is unknown. This proposal will clarify the role of alpha-synuclein in PD and normal CNS function and provide new potential therapeutic targets for the treatment of PD and other neurodegenerative disorders in which oxidative stress, excitotoxicity and central nervous system trauma have been implicated.Read moreRead less