New Approaches To Improve Thrombolysis In Ischaemic Stroke
Funder
National Health and Medical Research Council
Funding Amount
$586,076.00
Summary
Ischaemic stroke is caused by the presence of a blood clot in the brain. The removal of these clots is achieved using an enzyme called tissue-type plasminogen activator (t-PA). While this agent is effective if given to patients within 4.5h of stroke onset, delayed administration can cause cerebral bleeding. This project is to understand how t-PA promotes these unwanted effects in the brain and to devise novel approaches to extend the time window of t-PA administration in these patients.
Glia And The Progression Of Parkinson's Disease: Bystanders Or Villains?
Funder
National Health and Medical Research Council
Funding Amount
$534,838.00
Summary
Parkinson's disease (PD) is a chronic and progressive neurodegenerative disease with no cures or effective treatments. We know where in the brain PD begins but how it spreads to affect more and more cells is unknown. This lack of understanding has been a barrier to treatment development. In this project we will use new models that will enable unprecedented insight into this process of disease spreading, and in doing so will reveal new targets for therapeutic development.
Mechanisms Of PTEN Regulation By Ndfip1 And Their Biological Consequences For Neuron Survival During Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$686,640.00
Summary
We have discovered a new protein (Ndfip1) that protects brain cells from death after brain injury from trauma and stroke. We will investigate why this protein is activated only in some, but not in other, brain cells after injury. In this application, we will study the mechanisms behind neuron protection, and use this information to explore how to increase the number of brain cells activating Ndfip1.
Metabolism And Neurotoxicity Of Hemin And Hemin-derived Iron
Funder
National Health and Medical Research Council
Funding Amount
$346,400.00
Summary
Stroke is a leading cause of death and disability in industrialised countries. Much of the brain damage that follows a hemorrhagic stroke is attributable to the presence of free iron which mediates oxidative stress in brain cells. This iron originates from hemin, which in turn is derived from the hemoglobin in extravasated blood cells. The fact that iron is freed from hemin in the post-stroke period makes it an attractive therapeutic target. However, remarkably little is known about the metaboli ....Stroke is a leading cause of death and disability in industrialised countries. Much of the brain damage that follows a hemorrhagic stroke is attributable to the presence of free iron which mediates oxidative stress in brain cells. This iron originates from hemin, which in turn is derived from the hemoglobin in extravasated blood cells. The fact that iron is freed from hemin in the post-stroke period makes it an attractive therapeutic target. However, remarkably little is known about the metabolism of hemin by the different types of brain cells. The present project investigates the metabolism and neurotoxicity of hemin in brain cells and will examine the capacity of potential therapeutic agents to protect brain cells from hemin toxicity. The data obtained from this project will advance our understanding of the uptake and metabolism of hemin by the four main types of brain cell, and the factors that are likely to be involved in the neurotoxicity of hemin-derived iron following hemorrhagic stroke. The study will also provide data concerning the relative effectiveness of potential therapeutic agents, and information concerning the cell types, time points and aspects of hemin metabolism that are most effectively targeted by these agents. Such advances will guide the development of therapeutic approaches that are directed at minimising the brain damage which results from hemin-derived iron in humans.Read moreRead less
Growth factors are essential molecules for normal brain development. Variations in the amount of the different growth factors have been implicated in such diseases as AlzheimerÍs and ParkinsonÍs disease. This project will study the precursor of a growth factor known as brain derived neurotrophic factor (BDNF) and what specific roles the precursor might play in brain development.
Cellular Regulation Of Tooth Matrix Deposition And Remineralisation
Funder
National Health and Medical Research Council
Funding Amount
$124,530.00
Summary
Caries is one of the most prevalent of all human diseases. It has a very significant impact on the health budget of a nation apart from its effect on the individual concerned. In recent years there has been a growing recognition that healing or re-mineralisation protocols for the treatment of carious lesions in dentine are possible, rather than just relying on surgical removal of the diseased tissue and placement of restoratives. This project proposes to investigate a strategy for deliberately s ....Caries is one of the most prevalent of all human diseases. It has a very significant impact on the health budget of a nation apart from its effect on the individual concerned. In recent years there has been a growing recognition that healing or re-mineralisation protocols for the treatment of carious lesions in dentine are possible, rather than just relying on surgical removal of the diseased tissue and placement of restoratives. This project proposes to investigate a strategy for deliberately stimulating cellular reparative processes for the treatment of this disease. It is expected that the outcomes from this research will have a major influence on the techniques and materials used to treat this disease. They will potentially have a very broad application from the paediatric to the geriatric sectors of the dental profession.Read moreRead less
A Novel Mechanism For The Maintenance Of Catecholamine Synthesis
Funder
National Health and Medical Research Council
Funding Amount
$356,250.00
Summary
Stress causes an acute response that prepares us for flight or a fight and an adaptive response that requires days to establish. The catecholamines, including adrenaline, noradrenaline and dopamine are critical to both the acute and adaptive stress responses. They are secreted from cells at the level of the nervous system and the adrenal gland. We all respond differently to stress and if we do not cope we can become hypertensive or depressed. These pathologies require drug management and the dru ....Stress causes an acute response that prepares us for flight or a fight and an adaptive response that requires days to establish. The catecholamines, including adrenaline, noradrenaline and dopamine are critical to both the acute and adaptive stress responses. They are secreted from cells at the level of the nervous system and the adrenal gland. We all respond differently to stress and if we do not cope we can become hypertensive or depressed. These pathologies require drug management and the drugs all affect the catecholamine systems. Tyrosine hydroxylase controls catecholamine synthesis and it is activated in both the acute and adaptive phases of the stress response in order to replace catecholamines that have been secreted. Tyrosine hydroxylase is activated by protein phosphorylation in the acute phase and by the synthesis of new tyrosine hydroxylase in the adaptive phase. We have now discovered an additional and novel phase that we refer to as sustained tyrosine hydroxylase activation. This phase spans at least the period between the acute (mins) and adaptive phases (days). It involves the sustained phosphorylation of tyrosine hydroxylase and its mechanism appears to differ from the other two phases. In this project we will answer three questions. Does sustained tyrosine hydroxylase activation: 1 Occur in response to many stimuli and in many catecholamine cell types? 2 Occur by a single mechanism, different to the other phases, in all circumstances? 3 Play a role in the control of blood pressure and depression? This project will provide fundamental data about the mechanisms and consequences of sustained tyrosine hydroxylase activation, which is a part of the stress response not previously discovered. The data may impact on the way we design drugs to control stress responses, including antidepressants and antihypertensives.Read moreRead less