Role Of SOCS 3 In Regulating Oligodendroglial Phenotype In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$419,187.00
Summary
The response of nerve cells, known as oligodendrocytes, to an inflammatory insult dictates the severity of demyelinating diseases such as multiple sclerosis (MS). We have previously discovered that a key protein in this response is the cytokine leukaemia inhibitory factor (LIF) which, by activating the LIF receptor expressed on these cells, limits their death and reduces the clinical impact on animal models of MS. However, the therapeutic benefit of LIF is incomplete and we do not completely und ....The response of nerve cells, known as oligodendrocytes, to an inflammatory insult dictates the severity of demyelinating diseases such as multiple sclerosis (MS). We have previously discovered that a key protein in this response is the cytokine leukaemia inhibitory factor (LIF) which, by activating the LIF receptor expressed on these cells, limits their death and reduces the clinical impact on animal models of MS. However, the therapeutic benefit of LIF is incomplete and we do not completely understand the mechanisms by which LIF exerts these effects. To maximise the treatment potential of LIF we need to understand how LIF receptor signaling is modulated in the nervous system. An important protein known to regulate the activity of LIF and of other cytokines in other organs of the body is the suppressor of cytokine signaling 3 (SOCS 3) molecule. We have recently shown that the expression of SOCS 3 is increased in an animal model of MS, indicating that it is likely to modulate the activity of LIF in this context. We plan to investigate the nature of this regulation. SOCS 3 might limit the efficacy of LIF but it could also limit the deleterious effect of unbridled LIF receptor signaling. To distinguish between these possibilities, we plan to study the impact of demyelinating disease in animals in which SOCS 3 is either deleted or overexpressed in oligodendrocytes. In this way, we should be able to learn how to optimise the therapeutic potential of LIF in MS and related nervous system diseases.Read moreRead less
A Role Of Sortilin In The Development Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Summary
Alzheimer’s disease is the most common form of dementia and is caused by both environmental and genetic variations. With aging, a toxic peptide accumulates in the brain and causes loss of memory and cell death. This study aims to elucidate how the toxic peptide is generated and how its precursor trafficks within nerve cells.
Implications Of Retinal Neurodegeneration In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$602,213.00
Summary
Recent research has shown that “early signs” of Alzheimer ’s disease (AD) can be detected in the eyes. My research focus is to determine which particular changes in the retina are associated with AD. I will also investigate if blocking the production of beta amyloids (proteins produced in AD) in the eye will indeed help reduce their load in the brain and hence delay the onset of AD. Results from this research maybe used for early diagnosis and future medicinal studies that target the eye in AD.
Sortilin Forms A Complex With APP And BACE To Regulate Abeta Production
Funder
National Health and Medical Research Council
Funding Amount
$208,910.00
Summary
Alzheimer's disease is a neurodegenerative disorder which is highly prevalent in aging population. Amyloid beta is a toxic peptide derived from a metabolic processing of its precursor amyloid precursor protein (APP). This project will examine how a novel protein called sortilin interacts with APP and its processing enzyme and how the toxic peptide is produced. Understanding the trafficking of APP and beta-secretase ?BACE? regulated by sortilin may help understanding how Alzheimer's disease is de ....Alzheimer's disease is a neurodegenerative disorder which is highly prevalent in aging population. Amyloid beta is a toxic peptide derived from a metabolic processing of its precursor amyloid precursor protein (APP). This project will examine how a novel protein called sortilin interacts with APP and its processing enzyme and how the toxic peptide is produced. Understanding the trafficking of APP and beta-secretase ?BACE? regulated by sortilin may help understanding how Alzheimer's disease is developed.Read moreRead less
Neuroprotective Functions Of Autophagy Regulators In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$434,644.00
Summary
The accumulation of the beta amyloid protein has a central role in AD and enhancing its removal improves memory loss in animal AD models. This project builds on my recent finding of regulators of a cell housekeeping system, “autophagy” which accelerate removal of beta amyloid in cells. This study will advance knowledge into the protective functions of the autophagy regulators in reducing AD symptoms. Findings from this work might provide the basis for developing effective anti-AD therapeutics.
Use Of The P75NTR Extracellular Domain As A Therapeutic Target For The Treatment Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$733,633.00
Summary
AlzheimerÍs disease is the most common form of dementia and is caused by both environmental and genetic variations. With aging, a toxic peptide accumulates in the brain and causes loss of memory and cell death. This study aims to elucidate how the toxic peptide is generated and how to remove it in order to prevent and treat the disease.
The Characterisation Of The Mechanism Of Beta Amyloid Toxicity In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$94,430.00
Summary
Alzheimer�s disease (AD) is the most common form of dementia and is characterised by the beta amyloid peptide (A_) found in plaques in the brain. A structural transition to aggregated/ oligomeric forms of A_ is accompanied by a gain of toxicity. In this study the biological and biophysical characterisation of a variety of A_ peptides will be performed. The study will also use oligomers from cell culture media and brain tissue that have been influential in AD research but poorly characterised.
IRON EXPORT PROTEIN FAILURE IN PARKINSONISM AND DEMENTIA
Funder
National Health and Medical Research Council
Funding Amount
$843,352.00
Summary
We recently discovered a novel relationship between the Alzheimer’s amyloid precursor protein (APP) and tau, and that both proteins play a role in regulating iron levels in the brain. We predict that a loss or multiple failures in these iron-regulating systems could foster a toxic iron accumulation in brain, leading to the development of diseases with dementia such as Alzheimer’s and Parkinson’s diseases. We hope to gain a better understanding of their mechanism of action and propose that this p ....We recently discovered a novel relationship between the Alzheimer’s amyloid precursor protein (APP) and tau, and that both proteins play a role in regulating iron levels in the brain. We predict that a loss or multiple failures in these iron-regulating systems could foster a toxic iron accumulation in brain, leading to the development of diseases with dementia such as Alzheimer’s and Parkinson’s diseases. We hope to gain a better understanding of their mechanism of action and propose that this pathway is a target for therapeutic intervention.Read moreRead less