The PDZ Scaffold NHERF-1; A Novel Regulator Of Astrocyte Function?
Funder
National Health and Medical Research Council
Funding Amount
$444,500.00
Summary
Astrocytes are a vital cell type in the human brain. They provide nutrients to neurons, remove toxic chemicals such as glutamate (a neurotransmitter), as well as stabilising the levels of molecules such as water and ions such as sodium, bicarbonate and potassium. Astrocytes perform all these tasks by means of specialised protein molecules called transporters that are embedded in their cell membranes. These transporters are not uniformly distributed; they are positioned in those parts of the astr ....Astrocytes are a vital cell type in the human brain. They provide nutrients to neurons, remove toxic chemicals such as glutamate (a neurotransmitter), as well as stabilising the levels of molecules such as water and ions such as sodium, bicarbonate and potassium. Astrocytes perform all these tasks by means of specialised protein molecules called transporters that are embedded in their cell membranes. These transporters are not uniformly distributed; they are positioned in those parts of the astrocyte membranes where the particular biological job has to be performed. How are they targeted to, and retained in these places? We have preliminary data suggesting that a specialised protein called NHERF-1, can bind a group of these proteins, called glutamate transporters, thereby anchoring them to the skeleton of the cell. If we are correct then we should be able to manipulate this interaction, both in live brain tissues, and in simple cell culture systems, using a variety of physiological and molecular biology techniques. If we are correct in our hypothesis, then our findings will have immense value in trying to reduce damage that occurs in human brains in conditions such as strokes, where a breakdown in the control of glutamate around neurons causes extensive and irreversible brain damage.Read moreRead less
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.
Modifying Brain Excitabilty By Upregulating The KCC2 Chloride Transporter
Funder
National Health and Medical Research Council
Funding Amount
$535,662.00
Summary
Brain activity depends upon the fine balance between neuronal excitation and inhibition. When this balance is lost, debilitating seizures can result, such as occurs in epilepsy. We have developed a new gene manipulation approach to enhance neuronal inhibition and prevent seizures in mice. We will examine the physiological mechanisms underlying this effect, and we propose that we can also use this genetic switch to stop the progression into epilepsy that occurs following a brain trauma.
Unraveling the role of N-acetyl-aspartate in normal brain function and disease. The purpose of this project is to define the role of the predominating brain chemical N-acetyl-aspartate for normal nerve cell function and as toxic agent causing neurological illness and severe mental health problems. Findings of this research will enhance the design of novel therapies involving pharmacological and genetic treatment.