Brain Metal Neurochemistry: Mechanism-driven Drug Discovery For Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
Alzheimer’s disease (AD) is a complex disease where certain proteins congeal in the brain and metals accumulate. This project investigates the function of the proteins in microscopically transporting the metals. It will also look for tests that predict the onset of AD by measuring iron and iron related proteins by using special brain imaging (MRI), and measurements in spinal fluid. Finally, it will test drug candidates that target the metals, in animal models of AD, and in early clinical trials.
Huntington’s disease (HD) is a devastating neurodegenerative disorder which shares several features with Alzheimer’s and Parkinson’s disease (i.e. dementia-like cognitive deficits). There is currently no cure for HD. Using a mouse model of HD and a combination of relevant drugs (i.e. N-Acetylcysteine and deferiprone) targeting two distinct levels of the cascade of events leading to HD, we will slow down the progression of the disease and correct dysfunctions within the brain.
Brain Iron Imaging For Alzheimer’s Disease (AIBL-ADIRON Study)
Funder
National Health and Medical Research Council
Funding Amount
$1,227,885.00
Summary
Iron accumulation in the brain is linked to Alzheimer's disease. New Magnetic Resonance Imaging scans allow us to painlessly image the brain and measure its size and iron concentration. In this project more than 330 volunteers over 60 will be scanned every 18 months over 3 years. We will determine if those subjects with higher iron concentration in their brain have a smaller brain and worse performance in this period. This will confirm a role for iron in Alzheimer's as a new treatment target.
Metal-mediated Mechanisms And Therapeutic Approaches For Treating Brain Injury Across Age
Funder
National Health and Medical Research Council
Funding Amount
$1,229,769.00
Summary
This grant will examine the role of zinc and iron in the neuronal changes that occur following brain injury, with a specific focus on the role of these metals in functional outcomes. We will also examine how the role of these metals changes across the normal lifespan, and also whether these metal changes are consistent across different types of brain injury. Finally, we will examine the therapeutic potential of zinc- and iron-targeted compounds.
Lipophilic Iron Chelators As Potential Therapeutic Agents In Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$616,537.00
Summary
The impaired coordination and tremors experienced by the 64,000 Australians with Parkinson’s disease make managing life at work and home difficult. With 240,000 Australians projected to be living with Parkinson’s disease by 2033, the discovery of agents that slow or stop disease progression is urgent. Iron in the brain has been implicated in Parkinson’s disease. In this project, the performance of new low toxicity agents in altering brain iron distribution will be studied as potential drugs for ....The impaired coordination and tremors experienced by the 64,000 Australians with Parkinson’s disease make managing life at work and home difficult. With 240,000 Australians projected to be living with Parkinson’s disease by 2033, the discovery of agents that slow or stop disease progression is urgent. Iron in the brain has been implicated in Parkinson’s disease. In this project, the performance of new low toxicity agents in altering brain iron distribution will be studied as potential drugs for Parkinson’s disease.Read moreRead less
Understanding The Contribution Of Iron In Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$601,263.00
Summary
Our group has discovered a novel role of amyloid precursor protein (APP) in cellular iron balance similar to another protein called ceruloplasmin (CP). Both, prevalently found in the brain, convert a damaging iron variety into the safer form. Disruption in either protein leads to cell death. We aim to establish how failure in APP and CP response may be detrimental to traumatic brain injury recovery. Understanding the iron role of APP and CP will lead to therapeutics to counter traumatic injury.
Ghrelin Receptor Signaling In The Brain Links Hunger To Mood And Motivation
Funder
National Health and Medical Research Council
Funding Amount
$721,909.00
Summary
Cells in the brain that respond to hunger may also promote obsessive compulsive behaviours often associated with mental illness, such as anorexia nervosa. This grant examines how the signals from the body inform the brain of hunger. Specially we examine if overactivity of hunger cells, in the absence of appropriate food intake can increase behaviours associated with mental illness.
Post-stroke Hyperglycaemia – Treatment With Exenatide In Acute Ischaemic Stroke (TEXAIS) Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,266,149.00
Summary
Raised blood glucose levels (hyperglycaemia) after a stroke is common. It reduces the efficacy of stroke treatments and results in worse outcomes. Insulin is not useful as a treatment for this as it causes frequent hypoglycaemia and does not improve clinical outcomes. Exenatide is a common diabetes drug that is simple to use and lowers blood glucose without hypoglycaemia. It will be tested in the Treatment with Exenatide in Acute Ischaemic Stroke (TEXAIS) trial.
DIET-INDUCED OBESITY ALTERS THE CENTRAL ACTIONS OF GHRELIN
Funder
National Health and Medical Research Council
Funding Amount
$38,599.00
Summary
Ghrelin is a hormone that primarily targets the brain to increase food intake and body weight. It has evolved to prevent starvation during periods of negative energy balance by promoting energy intake and storage. We have identified central ghrelin resistance in diet-induced obesity (DIO) as a novel disturbed neuroendocrine system that restricts excessive food intake. Therefore, a novel approach to treat DIO is to exploit or enhance these intrinsic mechanisms that restrict the development of obe ....Ghrelin is a hormone that primarily targets the brain to increase food intake and body weight. It has evolved to prevent starvation during periods of negative energy balance by promoting energy intake and storage. We have identified central ghrelin resistance in diet-induced obesity (DIO) as a novel disturbed neuroendocrine system that restricts excessive food intake. Therefore, a novel approach to treat DIO is to exploit or enhance these intrinsic mechanisms that restrict the development of obesity.Read moreRead less