The Role Of Central And Peripheral Synaptic Activity In The Developmental Death Of Motoneurons.
Funder
National Health and Medical Research Council
Funding Amount
$463,145.00
Summary
Information processing in the nervous system relies on the effective communication between neurons and their target cells which make up our neuronal circuitry. At the centre of all this is the synapse, the specialized contact between a neuron and its target cell, be it another neuron in the brain or a target organ such as skeletal muscle. Our primary goal is to determine how the formation of synaptic connections during development regulates neuronal survival. In this proposal we have focussed on ....Information processing in the nervous system relies on the effective communication between neurons and their target cells which make up our neuronal circuitry. At the centre of all this is the synapse, the specialized contact between a neuron and its target cell, be it another neuron in the brain or a target organ such as skeletal muscle. Our primary goal is to determine how the formation of synaptic connections during development regulates neuronal survival. In this proposal we have focussed on the neuromotor system as it is a well characterised part of the nervous system. During development, 50% of motoneurons die at a time when they are making contact with skeletal muscle, and when contacts onto motoneurons by other neurons are being established. We believe that the formation of effective synaptic contacts onto motoneurons, as well as connections by motoneurons onto muscle are the key regulators of motoneuron survival. We are in a position to be able to address what regulates motoneuron death; as we have a number of mice which lack key molecules needed for the formation of specialisations that allow neuronal contacts to be made between motor neurons and their muscle, and with other neurons within the spinal cord. By examining the function of motoneurons, counting them and screening for molecular changes in these mice, we will be able to dissect out the mechanism of how a motoneurons' fate is determined during developmental motoneuron death. This research could help in developing strategies aimed at improving neuronal connections to improve neuronal viability. Our research will have important implications for our understanding about the basis of adult neuro-degenerative diseases, such as motor neuron disease and Alzheimer's, which are in part characterised by a molecular breakdown in neuronal connections that ultimately result in neuronal death.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120102961
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The role of the unfolded protein response in tau neurobiology and pathology. The main role of the protein tau is the stabilisation of the scaffolding of cells. In a group of dementias, tau forms abnormal clumps within the cells of the brain causing them to die. This project will investigate the cellular processes involved in normally preventing tau proteins from clumping and their role in the development of the abnormal tau clumps.
Investigating the neuroprotective actions of metallo-complexes. Metal-based drugs offer an exciting new approach to treatment of neurodegeneration. However, little is known about how cells metabolise these drugs: information that is critical for further drug development. This project will determine how metal-based drugs are metabolized by neuronal cells and how this may result in therapeutic benefit.
Gene-environment interactions mediating experience-dependent plasticity in the healthy and diseased brain. The aim of this project is to understand how genes and environment combine to affect susceptibility to various brain disorders, using models of human diseases and manipulating environmental factors such as mental and physical activity. The project's focus is on neurological and psychiatric disorders, including Huntington's disease, depression, schizophrenia and autism.
Axon Degeneration And Axon Protection In CNS Disease And Injury
Funder
National Health and Medical Research Council
Funding Amount
$389,120.00
Summary
One of the major reasons for the clinical symptoms of neurological diseases such as Alzheimer’s disease and Motor Neuron Disease is the loss of connections between the nerve cells. Nerve cells are connected by specialized processes called axons. In disease these processes can breakdown. This project specifically looks at how axons break down in disease and tests therapeutic strategies to protect them.
Uncovering The Molecular Mechanisms Behind Charcot-Marie-Tooth Disease
Funder
National Health and Medical Research Council
Funding Amount
$320,967.00
Summary
Charcot-Marie-Tooth disease (or CMT) is one of the most common disorders of the nervous system, affecting the normal function of the limbs and causing lifelong disabilities. There is currently no cure for CMT. The aim of this research is to develop a new model of CMT, which will allow us to uncover novel information about how the disease develops. This research will provide a better understanding of the disease and therefore provide valuable insight for the future generation of therapeutics.
A Novel Intracellular Roadblock To Cobalamin Utilization In Ageing And Alzheimer�s Disease
Funder
National Health and Medical Research Council
Funding Amount
$11,304.00
Summary
Vitamin B12 is required for red blood cell formation, DNA synthesis and normal neurological function. B12 deficiency contributes to age-related cognitive decline and Alzheimer�s disease. This research will provide important new information regarding the ageing process and the impact that brain changes associated with ageing and Alzheimer's disease have on B12 metabolism. It will provide important information related to the therapeutic potential of B12.
Role Of The Microglial Adaptor Molecule TYROBP In Alzheimer’s Disease Pathology
Funder
National Health and Medical Research Council
Funding Amount
$469,433.00
Summary
Immune activation characterizes Alzheimer’s disease (AD) brains; however, how it impacts AD progression is not understood. Our previous studies in AD brains identified the immune molecule TYROBP, pointing at both beneficial and detrimental effects triggered by this molecule. Here, we aim to understand in detail how TYROBP is involved in AD and how we can enhance its beneficial effects and decrease its unintended actions.
Defining The Function Of Apolipoprotein-D In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$457,231.00
Summary
Alzheimer's disease (AD) prevalence is rising and there is no curative treatment. Neurotoxic amyloid-beta peptide and concomitant lipid oxidation in the brain contribute to the cause of AD. We have identified a new pathway by which a protein called apoD may inhibit lipid oxidation in the AD brain. We will test the impact that changing apoD levels in neurons and in genetically modified mice has on neuron stress and AD-like characteristics. This may reveal new avenues to prevent or treat AD.