Control Of Catecholamine Synthesis And Secretion By Angiotensin II.
Funder
National Health and Medical Research Council
Funding Amount
$271,650.00
Summary
In the stress response the catecholamines, including adrenaline, are secreted by the adrenal gland and the brain. This leads to the synthesis of new catecholamines in order to replace those that were lost. Synthesis of catecholamines is controlled by the activity and the amount of the enzyme tyrosine hydroxylase. Catecholamine synthesis and secretion is therefore a fundamental physiological process. This can be controlled by a number of mechanisms, including hormones such as angiotensin II. Angi ....In the stress response the catecholamines, including adrenaline, are secreted by the adrenal gland and the brain. This leads to the synthesis of new catecholamines in order to replace those that were lost. Synthesis of catecholamines is controlled by the activity and the amount of the enzyme tyrosine hydroxylase. Catecholamine synthesis and secretion is therefore a fundamental physiological process. This can be controlled by a number of mechanisms, including hormones such as angiotensin II. Angiotensin II has a number of functions including the control of blood pressure and body fluid homeostasis. Angiotensin II acts on the adrenal glands, the sympathetic nerves and the brain to produce these effects. It does so by increasing the secretion of catecholamines and these in turn modulate blood pressure and fluid homeostasis. The mechanism(s) whereby angiotensin II induces catecholamine secretion is not known, nor is it known how this leads to increased tyrosine hydroxylase activity and synthesis. The aim of this grant is therefore to determine how angiotensin II induces the activation of tyrosine hydroxylase, the secretion of catecholamines and the synthesis of new tyrosine hydroxylase. The significance of this work is that it will allow us to better understand how angiotensin II works and it will provide insights into the generation and control of hypertension and the mechanisms of the stress response. It is known that the pathways involved in angiotensin II stimulation of catecholamine secretion can be blocked by inhibitors of protein kinases and this leads to a reduction in blood pressure. It is therefore likely that this work will have therapeutic implications.Read moreRead less
Regulation Of Amyloid-beta Production By Glycosphingolipid Synthesis Inhibition
Funder
National Health and Medical Research Council
Funding Amount
$549,925.00
Summary
Alzheimer's disease (AD) prevalence is rising and there is currently no curative treatment. Production of neurotoxic amyloid-beta peptide (Abeta) in the brain is thought to be one causative factor in AD. We have recently discovered a new drug that alters lipid levels in cell membranes and potently inhibits Abeta production by neurons. We will define precisely how this drug works and examine its potential to reduce Abeta accumulation in the brains of mice genetically engineered to mimic AD.
Amyloid Precursor Proteins Novel Role In Alzheimers Disease Through Regulating Neuronal Iron Homeostasis.
Funder
National Health and Medical Research Council
Funding Amount
$949,667.00
Summary
Our group has discovered a novel role of amyloid precursor protein (APP) in cellular iron balance. The smallest form of APP, prevalently found in the brain, is able to convert a damaging iron variety (Fe2+) into the safer Fe3+. Alternative, larger, forms of APP are found to inhibit this effect. This project will establish how APP controls iron homeostasis within brain neuronal cells and how this activity is impaired in disease, thus development a mechanism for diagnostic tests and therapeutics.
Modulation Of Calcium Signalling By Acetylcholine In The Basolateral Amygdala
Funder
National Health and Medical Research Council
Funding Amount
$266,748.00
Summary
The amygdala is an area of the brain involved in assigning emotional significance to sensory stimuli. This grant examines the cellular processes involved in making these associations. Specifically, it studies the relationship between two signalling molecules implicated in association learning, acetylcholine and calcium. This research will test hypotheses of memory formation and provide insight into disorders linked to detrimental emotional associations, such as anxiety and addiction.
Modulation And Trafficking Of SK Channels In The Lateral Amygdala
Funder
National Health and Medical Research Council
Funding Amount
$260,980.00
Summary
The amygdala is a brain structure that underlies emotional processing. Malfunctions in emotional processing are thought to be the cause of anxiety disorders. Understanding amygdala physiology is thus vital for developing therapies to treat these disorders. We have recently found a novel role for an ion channel in controlling amygdala excitability. In this grant we will investigate how this ion channel is modulated, which will elucidate a novel way in which activity in the amygdala is regulated.
Role Of ABCA-G Transporters In Neuronal Cholesterol Regulation And Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$557,582.00
Summary
Alzheimer's disease (AD) prevalence is rising and the contributing factors are poorly understood. Recent research shows that cholesterol regulates the production of neurotoxic amyloid-beta peptide (Abeta). We will study a class of proteins, ABC transporters, that we believe regulate neuronal cholesterol and Abeta metabolism. We will use isolated brain cells, human brain tissue and genetically engineered mice in order to define how cholesterol influences AD and identify new treatment options.