Complement Activation As A Therapeutic Target And Clinical Biomarker For Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$497,941.00
Summary
Parkinson’s disease is the second most common neurological disease in Australia, yet there is no treatment to slow disease progression. Our study is investigating inflammation within the brain as a major contributing factor in Parkinson’s disease. We will examine this inflammatory pathway in human patients suffering from Parkinson’s, and will test a novel anti-inflammatory drug in animal models of Parkinson’s disease, in order to identify a novel treatment to reduce disease pathology.
Preclinical Development Of Complement C5aR Antagonists For The Treatment Of Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$593,326.00
Summary
There is no cure for Motor Neuron Disease (MND) resulting in 2 Australian’s dying each day. Modification of the inflammation is one potential means of slowing MND. Our research team has identified a new series of potent anti-inflammatory compounds that may have potential to treat this disease. Our project will test these compounds in animal models of MND, and validate their usefulness in human MND samples. Ultimately, this work may contribute to the discovery of a new treatment for MND.
Therapeutic Targeting Of Neuroinflammation To Slow The Progression Of Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$463,652.00
Summary
My research has identified key components of our immune system, that can worsen disease in conditions such as Parkinson’s disease and motor neuron disease. I hope that exploring these components in animal models, and patients suffering from these diseases, my group can identify new therapeutic drug candidates that can be progressed in clinical trials. Ultimately, this may lead to new treatments to reduce disease burden in patients suffering from these neurodegenerative conditions.
Harnessing The Human Postmortem Brain To Elucidate Changes In FK506 Binding Protein (FKBP5) In The Neuropathology Of Severe Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$392,052.00
Summary
The postmortem human brain is a unique source to search for the pathological basis of severe psychiatric disorders including major depression, bipolar disorder and schizophrenia. Postmortem tissues are however being underutilised. This project will apply a selection of powerful biochemical measuring techniques to postmortem human brain tissues to uncover the molecular pathways of severe psychiatric disorders, which is knowledge that can lead to better treatments, preventions and cures.
Modulating Beta-amyloid Aggregation And Toxicity With Natural Metal-binding Proteins
Funder
National Health and Medical Research Council
Funding Amount
$399,243.00
Summary
Alzheimer's disease (AD) is a devastating disorder that afflicts millions of people worldwide. It is well established that the small peptide beta-amyloid, has a direct and important role in the development of AD. This project will investigate the ability of a small naturally occurring metal-binding protein to block the toxic actions of beta-amyloid.
The Role of Amyloid Protein Precursor in Mammalian Copper Transport. The knowledge gained from this investigation will help us to develop new medicines for the treatment of debilitating and ever more prevalent age-related neurodegenerative diseases and will help us to illuminate the role of metals in the ageing process itself. Apart from the obvious economic and social benefits in extending the productive lifetime of its citizens, the outcomes of this project have clear commercial applications. ....The Role of Amyloid Protein Precursor in Mammalian Copper Transport. The knowledge gained from this investigation will help us to develop new medicines for the treatment of debilitating and ever more prevalent age-related neurodegenerative diseases and will help us to illuminate the role of metals in the ageing process itself. Apart from the obvious economic and social benefits in extending the productive lifetime of its citizens, the outcomes of this project have clear commercial applications. We anticipate that there will be patents that will ensue from the programme, which will be licensed to Australian interests, and contribute to the national revenue in the biotechnology and pharmaceutical sector.Read moreRead less
Neural Copper Homeostasis: the role of the Alzheimer Amyloid-beta Precursor Protein. Alzheimer's disease (AD) is creating a growing burden upon Australian medical resources. Copper plays an important role in the development of AD, and drugs designed to adjust brain copper levels are being tested for AD treatment and show therapeutic benefits. This project will determine how copper is involved in AD so that more effective drugs can be developed. Focus will primarily be on copper-binding proteins ....Neural Copper Homeostasis: the role of the Alzheimer Amyloid-beta Precursor Protein. Alzheimer's disease (AD) is creating a growing burden upon Australian medical resources. Copper plays an important role in the development of AD, and drugs designed to adjust brain copper levels are being tested for AD treatment and show therapeutic benefits. This project will determine how copper is involved in AD so that more effective drugs can be developed. Focus will primarily be on copper-binding proteins central to AD, including amyloid-beta, and their role in AD development. Upon completion of this project, we expect to better understand neural copper metabolism in health and in AD pathology, with outcomes directly applicable to therapeutic AD intervention.Read moreRead less
Astrocyte-Neuron Communication: Unravelling The Role Of Astrocytes In The Modulation Of Neuronal Circuits
Funder
National Health and Medical Research Council
Funding Amount
$403,064.00
Summary
Astrocytes, a type of glial cell, are the most numerous cell type in the brain. They outnumber their neuronal counterparts by ten times and make up almost 90% of adult brain weight. They were originally thought to have only a supportive role in brain metabolism and the regulation of brain blood flow. It is now known that they also modulate neurons and their synapses through release of vesicles containing specific substances and have key roles in some neuropathic (e.g. pain and epilepsy) and neur ....Astrocytes, a type of glial cell, are the most numerous cell type in the brain. They outnumber their neuronal counterparts by ten times and make up almost 90% of adult brain weight. They were originally thought to have only a supportive role in brain metabolism and the regulation of brain blood flow. It is now known that they also modulate neurons and their synapses through release of vesicles containing specific substances and have key roles in some neuropathic (e.g. pain and epilepsy) and neurodegenerative states (e.g. Alzheimer's disease, Parkinson's disease, and multiple sclerosis). Many of these diseases are associated with a pathological astrocyte process known as 'reactivity'. This process remains enigmatic, resulting in so-called reactive gliosis, a reaction characterized by changes in gene expression, cell enlargement and changes in cell shape, and, in some cases, cell division. Most of the research on astrocyte reactivity has focused on the impairment of astrocyte metabolic activities. Comparatively little is known about the effect of reactive gliosis on so called 'newer' astrocyte roles such as their ability to interact with each other and nearby neurons using exocytosis of gliotransmitters (GTs: glutamate and ATP) and neurotrophic factors (NTFs: glial and brain derived neurotrophic factors). This project will both further investigate the normal mechanisms of astrocyte-neuron communication, and examine the effects of astrocyte reactivity on these mechanisms. The aim is to identify possible therapeutic targets to ameliorate the detrimental affects of neurodegeneration.Read moreRead less
The Role of Metals in the Biology of the Ageing Brain. Aims
1.To advance basic understanding of the interactions between cellular proteins and biologically important metals
2. To learn how these interactions change as the organism ages
3. To study the pathological results of aberrant metal biology using animal and cellular models of major age-dependent neurodegenerative disease.
In a rapidly ageing society, neurodegenerative disorders such as Alzheimer's and Parkinson's diseases will presen ....The Role of Metals in the Biology of the Ageing Brain. Aims
1.To advance basic understanding of the interactions between cellular proteins and biologically important metals
2. To learn how these interactions change as the organism ages
3. To study the pathological results of aberrant metal biology using animal and cellular models of major age-dependent neurodegenerative disease.
In a rapidly ageing society, neurodegenerative disorders such as Alzheimer's and Parkinson's diseases will present a medical and economic challenge demanding novel and powerful science. This research will lead both to deeper understanding of the basic mechanisms underlying such disorders and to tools for designing new and effective treatments.
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Investigating the intercellular trafficking of proteins and RNA and its relevance to neurodegenerative diseases. Alzheimer's and prion diseases are neurodegenerative disorders associated with protein misfolding. This project brings together similar features of these diseases using novel cell- and animal-based studies to develop a greater understanding of the molecular basis of these disorders.