The Involvement Of The Kynurenine Pathway In Blood Brain Barrier Disruption And Its Relevance For Neuroinflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$597,797.00
Summary
We aim to study the involvement of molecules deriving from the degradation of the essential amino acid tryptophan on the breakdown of the ñblood-brain barrierî (the cellular wall separating blood and brain) that is observed in several major brain diseases. Using specific drugs blocking the production or the effects of these toxic compounds we expect to be able to preserve the integrity of the blood brain barrier and so to limit brain inflammation and neuronal loss.
Targeting Early Cellular Damage During Secondary Degeneration Using Nanosphere-based Drug Delivery
Funder
National Health and Medical Research Council
Funding Amount
$424,407.00
Summary
After brain injury, there are no treatments to stop the spread of damage to intact tissue, a process involving different cell types and biochemical events. Clinical trials have targeted one event and have failed because large therapeutic doses are toxic and because combined treatments are needed to target different events. We will harness nanotechnology to target delivery of small, sustained doses of one or more drugs to specific cell types and biochemical events to stop the spread of damage.
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
Molecular And Cellular Mechanisms Of Vertebrate Brain Development
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
The essential steps in forming a normal functioning brain occur during life as an embryo. If these processes go haywire, there can be serious repercussions for life after birth. This project seeks to understand how the brain forms during embryonic stages so that better treatments and procedures can be developed to deal with developmental problems.
Glutamate is one of the major neurotransmitters in the brain. It plays a very important role in most brain functions such as the ability to learn and the development of memory, but the lack of control of glutamate concentrations in the brain also underlies many pathological changes that cause neurological disorders such Alzheimer's disease, disability following a stroke, motor neurone disease and Parkinson's disease. These diseases place an enormous social and economic burden on society and in o ....Glutamate is one of the major neurotransmitters in the brain. It plays a very important role in most brain functions such as the ability to learn and the development of memory, but the lack of control of glutamate concentrations in the brain also underlies many pathological changes that cause neurological disorders such Alzheimer's disease, disability following a stroke, motor neurone disease and Parkinson's disease. These diseases place an enormous social and economic burden on society and in order to better understand and treat these diseases it is important to understand some of the fundamental biochemical processes that underlie both normal and pathogical functions of the key neurotransmitter glutamate. This project will investigate how the concentrations of glutamate are tightly regulated to maintain normal brain function and also to avoid the potentially pathological consequences when these control mechanisms fail.Read moreRead less