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Developing A New Strategy For Treating Demyelinating Peripheral Diseases
Funder
National Health and Medical Research Council
Funding Amount
$496,250.00
Summary
Incomplete remyelination is a significant component of the persistent clinical disability of peripheral demyelinating neuropathy, contributing to conduction deficits and the secondary axonal damage. A crucial therapeutic challenge is to identify ways to promote remyelination. This project aims to develop a new strategy and a novel clinically relevant target for treating peripheral demyelinating neuropathy.
The Role Of P75 Neurotrophin Receptor-mediated Neurodegeneration Of Basal Forebrain Cholinergic Neurons
Funder
National Health and Medical Research Council
Funding Amount
$320,803.00
Summary
Alzheimer’s disease is a progressive neurodegenerative disorder characterized by clinical symptoms of memory deficits and cognitive function. It remains unclear what causes Alzheimer’s disease, but loss of a specific population of brain cells that are critical to cognitive function is generally accepted as a key feature of this condition. The aim of this project is to understand the mechanisms by which this cell loss occurs and how this relates to the loss of brain function.
I am a neuroscientist investigating the functional roles of neurotrophic factors in nervous diseases such as Alzheimer’s disease and spinal cord injury. I am also interested in the mechanisms of how these factors are involved in neural development.
Proteolytic Cleavage Of The P75 Neurotrophin Receptor Mediates Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$238,500.00
Summary
The p75 neutrotophin receptor (p75NTR) is a major inducer of nerve cell death, and is active in a wide range of neurodegenerative conditions, including Alzheimer's disease, motor neuron disease, multiple sclerosis, stroke and nerve trauma. This study aims to understand and to characterise the events that regulate this receptor. In particular, we will investigate the role that cleavage or controlled breakdown of the receptor plays in mediating its cell death activity. A fundamental aspect of this ....The p75 neutrotophin receptor (p75NTR) is a major inducer of nerve cell death, and is active in a wide range of neurodegenerative conditions, including Alzheimer's disease, motor neuron disease, multiple sclerosis, stroke and nerve trauma. This study aims to understand and to characterise the events that regulate this receptor. In particular, we will investigate the role that cleavage or controlled breakdown of the receptor plays in mediating its cell death activity. A fundamental aspect of this proposal is determining whether cleavage is due to presenilin-dependent activity, given that presenilin mutations have been demonstrated in most familial Alzheimer s disease cases. While this will increase our understanding of one of factors contributing to Alzheimer's disease, it also has much broader implications. A wide range of pharmaceuticals which regulate presenilin cleavage are already being developed and clinically tested for their efficacy in the treatment of Alzheimer s disease. Should our research demonstrate that p75NTR cleavage is the key process that regulates neuronal degeneration it will have major ramifications for approaches to the treatment of other p75NTR-associated neurodegenerative conditions.Read moreRead less
Modulation Of Neurotrophin Receptor Signaling: Understanding The Determinants And Phenotypic Consequences.
Funder
National Health and Medical Research Council
Funding Amount
$507,270.00
Summary
Peripheral nerves are complex structures consisting of motor and sensory neurons, their axons, and the cells that support them, Schwann cells. Peripheral neuropathy is a common neurological problem which covers many disorders of the peripheral nervous system. There are predominately two types of neuropathies: those where there is a primary loss or degeneration of neurons and-or their axons; and those where the Schwann cells are lost. These degenerative pathologies have prompted interest in the p ....Peripheral nerves are complex structures consisting of motor and sensory neurons, their axons, and the cells that support them, Schwann cells. Peripheral neuropathy is a common neurological problem which covers many disorders of the peripheral nervous system. There are predominately two types of neuropathies: those where there is a primary loss or degeneration of neurons and-or their axons; and those where the Schwann cells are lost. These degenerative pathologies have prompted interest in the potential of growth factors as a general therapy for peripheral neuropathy. The neurotrophins are a family of neuronal growth factors that influence many key aspects of neuronal development, as well as the maintenance of the mature peripheral nervous system. Work in cells in vitro and in animal models provides solid support for the hypothesis that the neurotrophins prevent neuronal death. However clinical trials testing the neurotrophins has led to variable results and side effects due to their many effects. To make these therapies useful, it is crucial to expand our knowledge about how they actually work and which of the many responses they induce actually produces their beneficial effect. This project aims to achieve this goal. I have identified a mechanism where neurotrophin signaling is selectively modulated in vitro. The aims of this project are to understand how this modulation of neurotrophin signaling is mediated, to identify the cellular substrates that are selectively activated and to determine what the biological consequences of this modulation are. Only through analyses such as these can we gain new insights into neurotrophin signaling and develop an understanding of how the activities of neurotrophins can be more precisely harnessed to generate new and more productive therapeutic approaches.Read moreRead less
Regulation Of P75 Death Signalling: How Neurotransmitter- And Neurotrophic- Signals Determine Cell Survival
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
Nerve cell survival is dependent on trophic support in the form of growth factors and synaptic input, both of which promote recovery after nerve injury. The survival pathways activated by growth factors are generally well characterised, whereas survival signals activated by synaptic activity are largely unexplored. This proposal aims to discover how synaptic activity prevents nerve cell death by looking at how synaptic activity inhibits the processes active in dying nerve cells.
Characterisation Of The Adiponectin Receptors - AdipoR1 And AdipoR2
Funder
National Health and Medical Research Council
Funding Amount
$445,158.00
Summary
The increasing incidence of cardiometabolic disease highlights an unmet need for novel therapeutic approaches. Greater understanding of the detail governing cardiometabolic function is required to provide a foundation to construct effective strategies. We will characterise 2 novel receptors that are important in the regulation and maintenance of cardiometabolic systems, seeking to identify strategies to enhance receptor, improve cardiometabolic function and reduce disease burden.
Molecular Pharmacology Of Chemokine Receptor Signalling In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$371,770.00
Summary
Molecular pharmacology is the study of how hormones, neurotransmitters and pharmaceuticals interact with our cells through receptors, which transfer a signal across the cell membrane to change the function of that cell. Chemokine receptors are recognised to play a role in the development of many cancers. Understanding how these receptors work has enormous implications for improving our ability to develop better anti-cancer treatments with fewer side effects.
Allosteric Targeting Of The Dopamine D2 Receptor: A Novel Approach For The Treatment Of Parkinson’s Disease And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$469,644.00
Summary
The dopamine D2 receptor is a brain protein that is the target for drugs that are used in the treatment of schizophrenia and Parkinson's disease (PD). In both cases the current drugs have significant side effects because they simply act to switch the receptor off or on respectively. We will focus on a new class of drugs that, because they act to tune up or tune down the activity of the D2 receptor, may be a safer more effective approach to treat these disorders.
The Novel CXCR4/CCR7 Heterodimeric Chemokine Receptor Is A Key Determinant Of Breast Cancer Metastasis.
Funder
National Health and Medical Research Council
Funding Amount
$461,252.00
Summary
Novel cellular receptor has been identified that works as a switch to turn on cellular functions that are responsible for the metastatic dissemination of cancer cell to distant organs. The make-up and regulatory mechanisms of this novel receptor will be studied together with its potential utility as the marker of metastatic breast cancer.