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
Exploring Scanning Ultrasound (SUS), A Novel Method To Treat And Prevent Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$765,708.00
Summary
We developed a novel scanning ultrasound (SUS) protocol that clears toxic protein aggregates and restores memory function in mouse models of Alzheimer's disease (AD), without the need for therapeutic agents. Here we aim to determine whether SUS has preventative potential, whether there are synergistic effects, and whether a therapeutic antibody combined with SUS leads to an enhanced therapeutic outcome. Together this will guide the development of an ultrasound therapy in AD patients.
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.
Understanding The Contribution Of Iron In Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$601,263.00
Summary
Our group has discovered a novel role of amyloid precursor protein (APP) in cellular iron balance similar to another protein called ceruloplasmin (CP). Both, prevalently found in the brain, convert a damaging iron variety into the safer form. Disruption in either protein leads to cell death. We aim to establish how failure in APP and CP response may be detrimental to traumatic brain injury recovery. Understanding the iron role of APP and CP will lead to therapeutics to counter traumatic injury.
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.
Neural Control Of Behavioural State And Cognition - Role Of Nucleus Incertus And Relaxin-3
Funder
National Health and Medical Research Council
Funding Amount
$600,771.00
Summary
Dementia and mental illness are significant social and economic burdens worldwide and knowledge of underlying causes and more effective therapies are required. Our research is using preclinical models to characterize a little studied neural network in the control of arousal states, rhythmic brain activity, and learning and memory. Our findings could advance the development of improved treatments for cognitive deficits in degenerative, age-related and psychiatric disorders.
Relaxin-3/RXFP3 Signalling And Regulation Of Affective Behaviour _ Studies In Normal/transgenic Mice
Funder
National Health and Medical Research Council
Funding Amount
$578,268.00
Summary
Mental illness is a significant social and economic burden worldwide and knowledge of the underlying causes and more effective therapies are required. Our research aims to use pre-clinical animal models to characterize a little studied brain neuronal network implicated in control of arousal and stress, which could lead to improved treatment of psychiatric disorders such as depression.
Molecular neurobiology of the GABAB receptor: Studies of heteromeric receptor function and signalling. The G protein-coupled receptor (GPCR) for the inhibitory transmitter gamma- aminobutyric acid (GABA) is a unique heterodimer. Molecular analyses will be undertaken to provide insights into its signalling mechanisms and functional regulation. Investigations employing point mutant and chimeric receptors will analyse how ligand binding to the extracellular domain of the GABA-BR1 subunit triggers ....Molecular neurobiology of the GABAB receptor: Studies of heteromeric receptor function and signalling. The G protein-coupled receptor (GPCR) for the inhibitory transmitter gamma- aminobutyric acid (GABA) is a unique heterodimer. Molecular analyses will be undertaken to provide insights into its signalling mechanisms and functional regulation. Investigations employing point mutant and chimeric receptors will analyse how ligand binding to the extracellular domain of the GABA-BR1 subunit triggers G protein-coupling to the intracellular portion of the GABA-BR2 subunit. Focus will be on different modes of GPCR signalling, including constitutive activity and roles for membrane and cytosolic regulatory proteins. Targeted studies of GABAB receptor subunits will provide new information on the mechanistic regulation of GPCR signalling.Read moreRead less
Novel cellular functions of the microtubule-associated protein tau: Physiological and pathological implications. The social and economic burden of Alzheimer's disease (AD) is enormous, and by 2040 more than 500,000 Australians will suffer from this disease. A key histopathological hallmark of this and many other related diseases are insoluble deposits of the protein tau. Research into novel functions of tau in signalling and transport (both of which are heavily compromised in diseased brains) wi ....Novel cellular functions of the microtubule-associated protein tau: Physiological and pathological implications. The social and economic burden of Alzheimer's disease (AD) is enormous, and by 2040 more than 500,000 Australians will suffer from this disease. A key histopathological hallmark of this and many other related diseases are insoluble deposits of the protein tau. Research into novel functions of tau in signalling and transport (both of which are heavily compromised in diseased brains) will be followed directly by assay development for tau-directed drug screening. The national benefit of this research is manifold by (a) patenting new data, (b) developing treatment strategies for an un-curable disease, and (c) establishing links to the growing Australian biotech industry (in addition to existing links to international pharmaceutical companies).Read moreRead less
The biological and pathological functions of TDP-43. The social and economic burden of neurodegenerative such as MND is enormous. A key histopathological hallmark of this and many other related diseases are deposits of the protein TDP-43. Our research aims at understanding its largely unknown functions, for example by generating transgenic animal models. These will form the base for the development for a TDP-43-directed drug treatment. The national benefit of this research is manifold: by deciph ....The biological and pathological functions of TDP-43. The social and economic burden of neurodegenerative such as MND is enormous. A key histopathological hallmark of this and many other related diseases are deposits of the protein TDP-43. Our research aims at understanding its largely unknown functions, for example by generating transgenic animal models. These will form the base for the development for a TDP-43-directed drug treatment. The national benefit of this research is manifold: by deciphering basic biological mechanisms, patenting new data, developing treatment strategies for un-curable and fatal disorders, and expanding links to Australian biotech and international pharmaceutical companies.Read moreRead less