Regulation Of The Beta-secretase (BACE1) By Glycosaminoglycans
Funder
National Health and Medical Research Council
Funding Amount
$561,212.00
Summary
Alzheimer's disease is the leading cause of dementia in the elderly. Because of the prolonged institutionalisation of patients, it is a major health care burden. This project aims to develop novel drugs which can treat Alzheimer's disease by inhibiting production of the protein which causes the neurodegeneration.
Mechanisms For Ageing Changes In The Hepatic Sinusoid
Funder
National Health and Medical Research Council
Funding Amount
$413,750.00
Summary
We recently discovered changes in the blood vessels of the liver that occur with old age that we have called pseudocapillarisation. These changes include thickening of the liver sinusoidal endothelium, deposition of basal lamina and collagen, and marked loss of specialized pores within the endothelium called fenestrations. These changes have profound effects on the transfer of many substrates including toxins, drugs, oxygen, hormones and lipids from the blood into the liver and thus may explain ....We recently discovered changes in the blood vessels of the liver that occur with old age that we have called pseudocapillarisation. These changes include thickening of the liver sinusoidal endothelium, deposition of basal lamina and collagen, and marked loss of specialized pores within the endothelium called fenestrations. These changes have profound effects on the transfer of many substrates including toxins, drugs, oxygen, hormones and lipids from the blood into the liver and thus may explain in part the fact that old age is the major risk factor for many diseases and adverse drug reactions. To further understand the mechanisms for these important ageing liver changes, we are proposing several studies. First, the effects of caloric restriction on the liver blood vessels will be studied because caloric restriction delays the primary ageing process. Second we will study the effects of ageing on F-actin, ATP, caveolin-1 and VEGF because these mechanisms have established roles in regulating the structure and function of the liver blood vessels and in particular their fenestrations. Finally we will determine whether VEGF can reverse the ageing changes in the liver blood vessels and stimulate the formation of new fenestrations within these blood vessels. Our research provides one mechanism for the inexorable association between old age and susceptibility to disease - based on primary ageing changes in the liver. As well as increasing our understanding of the cellular changes for ageing and the basic mechanisms involved in the regulation of the liver endothelial cells and their fenestrations, this proposed research will provide a foundation for the development of therapeutic interventions for the prevention and treatment of some age-related disorders.Read moreRead less
The Role Of Central Haemodynamics In Type 2 Diabetes Mellitus-related Brain Disease
Funder
National Health and Medical Research Council
Funding Amount
$899,704.00
Summary
Type 2 Diabetes Mellitus is associated with stiffening of major blood vessels which may allow the transmission of harmful pressure to the small vessels of the brain. This may in turn be responsible for damage to brain cells and a greater risk of dementia. This study will use state-of-the art techniques to test this theory. If true, it may open opportunities to reduce the risk of brain disease in diabetes by using therapies to reduce arterial stiffening.
DEVELOPMENT OF NOVEL THERAPEUTICS FOR DEMENTIA: Investigating Tailored Brain Stimulation Approaches For Dementia Prevention And Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$723,105.00
Summary
Dementia is a debilitating and devastating illness impacting significantly on sufferers, carers and the wider community. Current treatment approaches are limited in their effectiveness and alternative therapeutics are needed. My research will investigate the use of brain stimulation techniques for the treatment and prevention of dementia.
Therapeutic And Diagnostic Approaches For The Neurodegenerative Diseases
Funder
National Health and Medical Research Council
Funding Amount
$804,106.00
Summary
Diseases of the brain such as Alzheimer’s and Parkinson’s disease cause enormous socio-economic harm to Australia. They are a major cause of disability and the burden associated with mental illness is predicted to grow by almost 50% over the coming decade. Therefore there is an urgent need to develop new approaches to identify and treat these diseases. This Fellowship will be dedicated to creating new diagnostic methods and treatments for these diseases
A Population-based Study Of Cerebrovascular Mechanisms Underyling Gait, Balance And Cognition In Older People
Funder
National Health and Medical Research Council
Funding Amount
$528,330.00
Summary
Mobility problems, falls and dementia are among the major problems affecting older Australians with significant consequent disability. Treatment of such disorders carries an estimated annual cost of around 4 billion dollars. This study will examine the role of age-related brain changes in causing problems with walking, balance and cognitive abilities in the general community. The clarification of the role of the ageing brain in causing such disorders will guide efforts directed at preventing the ....Mobility problems, falls and dementia are among the major problems affecting older Australians with significant consequent disability. Treatment of such disorders carries an estimated annual cost of around 4 billion dollars. This study will examine the role of age-related brain changes in causing problems with walking, balance and cognitive abilities in the general community. The clarification of the role of the ageing brain in causing such disorders will guide efforts directed at preventing the occurrence of falls and dementia.Read moreRead less
SELECTIVE VULNERABILITY IN ALZHEIMER’S DISEASE AND RELATED DISORDERS: MECHANISM OF TAU PATHOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$1,072,324.00
Summary
Alzheimer’s disease and related dementias affect 230,000 people in Australia, with numbers expected to grow to 730,000 by 2050. The direct costs for health and residential care alone exceed $6.6 billion per annum. By identifying genes that protect degenerating neurons in the Alzheimer brain, a deeper understanding of the underlying processes will be gained and therapeutic targets will be defined that will assist in developing a therapy for a yet uncurable disease.
From Brain Maps To Mechanisms: Modelling The Pathophysiology Of Dementia
Funder
National Health and Medical Research Council
Funding Amount
$604,513.00
Summary
As the brain ages, the relationship between its structure and function also changes. In this study, I will use detailed computational modelling and extensive analyses of brain dynamics to improve interventional strategies by: 1. Characterising healthy and unhealthy brain dynamics during ageing; 2. Classifying the various subtypes of pathological dynamics; and 3. Predicting pathological neurodegeneration by identifying the earliest signs of perturbations in healthy ageing.
The Importance Of P38 MAPK Signalling In Aging-Related Ischaemic Intolerance And Failed Cardioprotection
Funder
National Health and Medical Research Council
Funding Amount
$496,302.00
Summary
Ischaemic heart disease is the leading cause of death in Australia, and will rise in coming years with the aging of our population. Our research shows aged hearts become less resistant to damage during ischaemia-heart attack, and insensitive to normally beneficial therapies. This project will identify molecular changes responsible for these changes. By understanding how age impairs the hearts defences, it may be possible to improve therapy of ischaemic heart disease in older patients.