The Role Of A Presenilin 2 Truncation (PS2V) In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$552,741.00
Summary
The Presenilin and APP proteins are centrally important in inherited, early onset Alzheimer's disease. We have discovered that a shortened form of Presenilin protein, "PS2V", appears to increase specifically the rate at which the APP protein is cleaved to produce the "Amyloid beta" protein fragment that is found in Alzheimer's disease brains. This occurs when brain cells are under oxidative stress. Understanding this process will facilitate development of appropriate therapeutic strategies for t ....The Presenilin and APP proteins are centrally important in inherited, early onset Alzheimer's disease. We have discovered that a shortened form of Presenilin protein, "PS2V", appears to increase specifically the rate at which the APP protein is cleaved to produce the "Amyloid beta" protein fragment that is found in Alzheimer's disease brains. This occurs when brain cells are under oxidative stress. Understanding this process will facilitate development of appropriate therapeutic strategies for the disease.Read moreRead less
Role Of Apolipoprotein D In Alzheimer's Disease And Frontotemporal Dementia
Funder
National Health and Medical Research Council
Funding Amount
$575,612.00
Summary
ApoD is a highly conserved lipocalin known for its antioxidant nature and role in regulation of inflammation. Oxidative stress and neuroinflammation are known to play a critical role in dementia. This project will study the association of apoD to inflammatory and oxidative stress markers in Alzheimer’s disease and Frontotemporal Dementia, two major forms of dementia. It will also examine the impact of apoD on disease pathology. Hence this project will lead us to therapeutic potentials of apoD.
The Role Of LIM Domain Kinase 1 In The Pathogenesis Of Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$565,531.00
Summary
Alzheimer’s disease is characterized by progressive loss of cognition. Few Australians have remained untouched by the effects of Alzheimer’s disease in their families or social circles. Unfortunately, there is no cure and current therapies are limited to modest symptomatic relief. This project will explore the role of a protein that regulates the structural integrity of brain cells in disease, and test if targeting this protein could prevent disease progression.
Does IRAP Contribute To Alzheimer's Disease Pathology?
Funder
National Health and Medical Research Council
Funding Amount
$743,042.00
Summary
Alzheimer’s disease is a progressive brain disease which is results in memory loss and cell death. All currently prescribed drugs treat the memory loss but are unable to stop the deterioration of brain cells. We have developed a class of drugs that reverse memory loss. These drugs target a protein called insulin-regulated aminopeptidase, IRAP. We recently found that these drugs also reduce the disease pathology. This research proposal aims to investigate the role of IRAP in the initiation or pro ....Alzheimer’s disease is a progressive brain disease which is results in memory loss and cell death. All currently prescribed drugs treat the memory loss but are unable to stop the deterioration of brain cells. We have developed a class of drugs that reverse memory loss. These drugs target a protein called insulin-regulated aminopeptidase, IRAP. We recently found that these drugs also reduce the disease pathology. This research proposal aims to investigate the role of IRAP in the initiation or progression of Alzheimer’s disease pathology.Read moreRead less
Inflammation plays both protective and damaging roles in Alzheimer’s disease (AD), so to identify a long lasting and effective treatment, it is important that we better understand the underlying processes. Our studies implicate a cytokine called interleukin-18 (IL-18) as a factor that accelerates AD pathology. Here we propose to study the mechanisms by which this cytokine alters basic cell biological functions and how these changes affect AD pathogenesis.
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.
Investigating Interleukin-37 As A Treatment And Biomarker For Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$677,857.00
Summary
Alzheimer’s disease (AD) is the defining healthcare condition of our generation. Finding asymptomatic at risk individuals at preclinical stages will allow initiation of therapies that will either slow or, preferably, stop the progression of the disease. Herein, we will study a protein called interleukin-37 as an early biomarker and treatment for AD.
Compromised Fetal Brain Development: Neurogenesis And The Potential For Therapeutic Intervention.
Funder
National Health and Medical Research Council
Funding Amount
$497,280.00
Summary
Lack of oxygen to the fetal brain during pregnancy is thought to be the main causes of brain injury in newborns. Some of these infants will suffer developmental and behavioural problems including cerebral palsy, schizophrenia and epilepsy. Currently, there is no effective treatment to redress these changes in brain development and this is one of the major challenges in perinatal medicine today. We have previously shown in a guinea pig model of chronic placental insufficiency (reduced oxygen and ....Lack of oxygen to the fetal brain during pregnancy is thought to be the main causes of brain injury in newborns. Some of these infants will suffer developmental and behavioural problems including cerebral palsy, schizophrenia and epilepsy. Currently, there is no effective treatment to redress these changes in brain development and this is one of the major challenges in perinatal medicine today. We have previously shown in a guinea pig model of chronic placental insufficiency (reduced oxygen and nutrient levels during pregnancy) that there is a reduction in neurons and in the connections between them. This may result from a reduction in number of newly generated neurons (neurogenesis), or an increase in neuronal death (apoptosis), or both. To develop therapeutic strategies to improve brain growth and ultimately functional recovery, we must understand the mechanisms which lead to these brain changes. In this project, we will use our guinea pig model to: 1) determine whether a suboptimal fetal environment decreases neuronal numbers by influencing neurogenesis, apoptosis or both, 2) study changes in the compromised brain environment which are likely to influence apoptosis and neurogenesis, 3) determine whether a suboptimal fetal environment has long-term effects on adult neurogenesis and 4) determine whether treatment with erythropoietin (Epo), a naturally occurring hormone, can resolve deficits in brain development and function. Epo is an exciting candidate as it is, or is in the process of being used to treat stroke and newborn asphyxiation. Epo has also been shown to prevent neuronal death and promote neurogenesis following brain injury. Understanding the mechanisms and finding effective treatments for brain damage is a vital area of endeavour if we are to help infants develop their maximum potential and reduce the enormous social, economic and educational burden which must be borne by the individual and society in general when things go wrong during pregnancy.Read moreRead less
Investigating Underlying Mechanisms Linking Type 2 Diabetes With Alzheimer’s Disease Pathology
Funder
National Health and Medical Research Council
Funding Amount
$701,950.00
Summary
With type-2 diabetes representing a major risk factor for neurodegenerative diseases such as Alzheimer's disease, it is important to understand the underlying mechanisms. This project will provide significant insight into how T2D impacts the brain with a focus on how deficiencies in brain inuslin signaling drives neurodegeneration. We will also evaluate novel inuslin like molecules at improving brain insulin siganling and preventing or slowing down the neurodegenerative process.
The Genetic And Environmental Determinants Of Amyloid Deposition In Older Individuals: An Amyloid Imaging Study Using The Twin Design
Funder
National Health and Medical Research Council
Funding Amount
$643,267.00
Summary
Alzheimer’s disease is characterised by the deposition of amyloid plaques in the brain. We don’t fully understand how amyloid deposition occurs and what contribution is made by genetic and environmental factors. Amyloid deposition in the brain can now be quantified during life using positron emission tomography. In this study, we will examine brain amyloid in twins, which will determine what proportion of the pathology is attributable to environmental factors that may be modifiable.