The role of P2X7 and P2X4 receptor mediated innate phagocytosis in pathogenesis and treatment of neurodegenerative diseases. This project will identify how inherited variation in two proteins of the brain can accelerate the removal of neurones and predispose to a range of neurodegenerative diseases. Knowledge of the biological basis of this finding will allow a search for new compounds which will slow and protect against this form of neurodegeneration.
Discovery Early Career Researcher Award - Grant ID: DE130100323
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The regulation by transcription factor phosphorylation upon the myelinating process. The project will investigate the novel molecular events that control the myelinating process, which is essential for normal nervous system function. Outcomes of this project may aid the development of novel interventions to improve control of demyelinating diseases, which represent a substantial socio-economic burden.
The Genetic Analysis of Neurological Diseases. Multiple sclerosis and Parkinson's are debilitating neurodegenerative diseases, which affect 16,000 and 80,000 Australians, respectively. Between them, these diseases cost the community $7.8 billion per annum, and there is no cure. This proposal will study the genes that influence a person's predisposition to developing these diseases, and what makes some people have particular characteristics. It will provide novel insights into the diseases themse ....The Genetic Analysis of Neurological Diseases. Multiple sclerosis and Parkinson's are debilitating neurodegenerative diseases, which affect 16,000 and 80,000 Australians, respectively. Between them, these diseases cost the community $7.8 billion per annum, and there is no cure. This proposal will study the genes that influence a person's predisposition to developing these diseases, and what makes some people have particular characteristics. It will provide novel insights into the diseases themselves and information that could help in the development of new and more effective drugs, and biomarkers to assist in the prediction of prognosis. Such advances would decrease the economic impact of these diseases and improve quality of life for those affected.Read moreRead less
Enhancing our understanding of metallochemistry in neurobiology with modern electron paramagnetic resonance (EPR) spectroscopy. Many neurological diseases involve protein accumulation that appears causally linked to abnormal levels of metal ions in the brain. This project will use a special technique called electron paramagnetic resonance to uncover how these metals interact with specific proteins at the molecular level and how drug treatments can modify these interactions.
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
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.
Multimodal retinal imaging provides "insight" into cerebrovascular ageing. Multimodal retinal imaging provides "insight" into cerebrovascular ageing. This project aims to develop a multi-modal imaging technology platform to simultaneously measure amyloid beta and its neurovascular sequelae to identify novel early biomarkers of ageing in the eye and brain. The growing ageing population is an increasing socioeconomic burden. The central nervous system is particularly susceptible to ageing, which i ....Multimodal retinal imaging provides "insight" into cerebrovascular ageing. Multimodal retinal imaging provides "insight" into cerebrovascular ageing. This project aims to develop a multi-modal imaging technology platform to simultaneously measure amyloid beta and its neurovascular sequelae to identify novel early biomarkers of ageing in the eye and brain. The growing ageing population is an increasing socioeconomic burden. The central nervous system is particularly susceptible to ageing, which is difficult to measure at its onset. Critically, as the eye is an easily accessible extension of the cortex, retinal imaging may be a non-invasive surrogate to assess ageing changes in the brain. Anticipated outcomes are a sensitive detector of neural ageing, improved preventative measures, reducing the socioeconomic burden of ageing, and improved quality of life.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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Prevention of age-related learning and memory dysfunction with novel compounds. This project will illuminate the fundamental brain changes that lead to age-related cognitive decline and to then test the validity of this as a novel therapeutic target. The expected outcome of this work will be a unique approach to the treatment of cognitive decline that will fill a significant unmet need within the community.