Apolipoprotein A-I-stimulated Secretion Of Apolipoprotein E By Human Foam Cell Macrophages.
Funder
National Health and Medical Research Council
Funding Amount
$201,208.00
Summary
Atherosclerosis is the disease which causes narrowings in arteries underlying such serious conditions as heart attack and stroke. A key component of the formation of atherosclerotic narrowings in arteries is the accumulation of fat-filled cells called foam cell macrophages. These foam cells can be stimulated to secrete a special molecule called apolipoprotein E (or apo E), which reduces the amount of atherosclerosis. We have found that we can stimulate foam cells to secrete this protein by addin ....Atherosclerosis is the disease which causes narrowings in arteries underlying such serious conditions as heart attack and stroke. A key component of the formation of atherosclerotic narrowings in arteries is the accumulation of fat-filled cells called foam cell macrophages. These foam cells can be stimulated to secrete a special molecule called apolipoprotein E (or apo E), which reduces the amount of atherosclerosis. We have found that we can stimulate foam cells to secrete this protein by adding to them another molecule called apo A-I. This project will investigate how apo A-I stimulates the foam cells to secrete apo E. In this way we will be able to regulate the secretion of apo E, and be able to increase its secretion. This may result in our being able to treat or prevent atherosclerosis.Read moreRead less
The Regulation Of Apolipoprotein E Secretion By Human Macrophages
Funder
National Health and Medical Research Council
Funding Amount
$516,078.00
Summary
One of the major inflammatory cells in the body, the macrophage, is involved in a number of diseases, including coronary disease. ApoE is made and released by macrophages and appears to protect against the inflammation of coronary disease and may affect other conditions, including Alzheimer's disease. We have discovered pathways regulating the production and release of apoE by macrophages, and in this project will study these pathways in great detail. By controlling the production of this import ....One of the major inflammatory cells in the body, the macrophage, is involved in a number of diseases, including coronary disease. ApoE is made and released by macrophages and appears to protect against the inflammation of coronary disease and may affect other conditions, including Alzheimer's disease. We have discovered pathways regulating the production and release of apoE by macrophages, and in this project will study these pathways in great detail. By controlling the production of this important molecule we may reduce our risk of heart disease, and may be able to treat a range of inflammatory conditions which currently untreatable.Read moreRead less
The Effect Of Human ApoE Isoforms And ApoE Receptors On The Clearance Of Oligomeric A 42 By Hepatocytes In Vitro
Funder
National Health and Medical Research Council
Funding Amount
$424,801.00
Summary
Alzheimer's disease (AD) is a progressive memory disorder. Increased production of a short peptide called amyloid- (A ) aggregates to form the sticky masses in the brains of AD patients. The amount of A in the brain is a balance between production and clearance. Surprisingly, we recently demonstrated that the liver clears the majority of A . These results connect AD and cardiovascular disease (CVD), enabling current CVD therapeutics to target A clearance by the liver.
The Role Of Endothelial Lipase In High Density Lipoprotein Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$130,550.00
Summary
Atherosclerosis is a major cause of death and disability in Australia. A high level of blood cholesterol increases the risk of developing atherosclerosis. This increase in risk is caused by the cholesterol that is carried in low density lipoproteins (LDL). However, not all cholesterol is bad. A proportion of the cholesterol in blood is carried in high density lipoproteins (HDL), which are powerful protectors against atherosclerosis. As not all HDL protect equally well against atherosclerosis, it ....Atherosclerosis is a major cause of death and disability in Australia. A high level of blood cholesterol increases the risk of developing atherosclerosis. This increase in risk is caused by the cholesterol that is carried in low density lipoproteins (LDL). However, not all cholesterol is bad. A proportion of the cholesterol in blood is carried in high density lipoproteins (HDL), which are powerful protectors against atherosclerosis. As not all HDL protect equally well against atherosclerosis, it is important to know how blood levels of HDL are regulated. In 1999 a new enzyme called endothelial lipase was discovered. Endothelial lipase dramatically decreases HDL levels in mice. The reason why this happens is not known. The main aims of this project are to work out how endothelial lipase decreases HDL levels and whether it decreases the levels of all HDL equally or whether it preferentially decreases the levels of certain types of HDL. The outcome of this project will establish how endothelial lipase affects the ability of HDL to protect against atherosclerosis in humans.Read moreRead less
Molecular & Neuropsychological Predictive Markers Of Cognitive Decline.
Funder
National Health and Medical Research Council
Funding Amount
$429,500.00
Summary
Alzheimer's disease (AD) is a major cause of dementia in the elderly. As populations worldwide are living longer the prevalence of AD is predicted to rise markedly and in addition to the huge emotional burden on families the economic implications to the community at large is severe. Thus our aging veteran population and their spouses are particularly vulnerable to this devastating disease. Recent developments in AD research have resulted in a number of therapeutic strategies being undertaken wit ....Alzheimer's disease (AD) is a major cause of dementia in the elderly. As populations worldwide are living longer the prevalence of AD is predicted to rise markedly and in addition to the huge emotional burden on families the economic implications to the community at large is severe. Thus our aging veteran population and their spouses are particularly vulnerable to this devastating disease. Recent developments in AD research have resulted in a number of therapeutic strategies being undertaken with several of these now in phase 2 clinical trials. However for these treatments to be most effective early diagnosis is crucial. Currently, definite diagnosis is restricted to post-mortem examination of the brain for the presence of characteristic neuropathological features. This project proposes to identify individuals at high risk of developing cognitive decline leading to AD by using a battery of biochemical, genetic and neuropsychological markers. This study builds on our earlier work which followed a cohort of memory complainers and demonstrated that subjects in this group have lower cognitive scores and an increased frequency of the genetic risk factor, the e4 allele of apolipoprotein E. Follow up of this well studied cohort with more sensitive and extensive neuropsychological tests together with other genetic and biochemical markers will be important in identifying those risk factors that have positive predictive value for cognitive decline thereby contributing towards enhancing the therapeutic efficacy of current symptomatic and future drugs directed at the cause of AD.Read moreRead less
Role Of ABCA-G Transporters In Neuronal Cholesterol Regulation And Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$557,582.00
Summary
Alzheimer's disease (AD) prevalence is rising and the contributing factors are poorly understood. Recent research shows that cholesterol regulates the production of neurotoxic amyloid-beta peptide (Abeta). We will study a class of proteins, ABC transporters, that we believe regulate neuronal cholesterol and Abeta metabolism. We will use isolated brain cells, human brain tissue and genetically engineered mice in order to define how cholesterol influences AD and identify new treatment options.