Mitochondrial Iron Overload And Friedreich's Ataxia: The Role Of Frataxin In Iron And Haem Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$285,990.00
Summary
Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. Recent studies using Baker's yeast have shown that the deletion of frataxin results in the accumulation of toxic iron in the mitochondrion. More recently, a variety of studies have shown that FA patients have iron loading within their cells. The iron build-up may cause severe damage. At present, the role of frataxin in mammalian mitochondrial iron metabolism is unknown. Our preliminary studies demonstrate that frataxin i ....Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. Recent studies using Baker's yeast have shown that the deletion of frataxin results in the accumulation of toxic iron in the mitochondrion. More recently, a variety of studies have shown that FA patients have iron loading within their cells. The iron build-up may cause severe damage. At present, the role of frataxin in mammalian mitochondrial iron metabolism is unknown. Our preliminary studies demonstrate that frataxin is down-regulated by either erythroid differentiation or the haem precursor protoporphyrin IX (Becker and Richardson, submitted). These data strongly suggest a role for frataxin in iron metabolism. In the present study we will continue to assess if frataxin plays a role in the way cells handle iron. Using a unique model of mitochondrial iron overload developed in my lab (Richardson et al. (1996) BLOOD 87:3477), we will extensively investigate the iron metabolism of the mitochondrion in order to determine the function of frataxin and its role in Friedreich's ataxia. In addition, we have developed a series of new drugs known as iron chelators that can enter the mitochondrion due to their high lipid solubility (Becker and Richardson 1999 J. Lab. Clin. Med. 134:510). These latter drugs are far more effective than the chelator currently used to treat iron overload, desferrioxamine (DFO). Indeed, our chelators have been designed to result in high iron chelation efficacy but low toxicity (see Becker and Richardson, 1999). This exciting research may be crucial in understanding the development of FA and in creating new therapies such as the use of iron chelators.Read moreRead less
Restoration Of Diabetes Associated Cognitive Deficits Through The Modulation Of Cerebrovascular Integrity
Funder
National Health and Medical Research Council
Funding Amount
$430,998.00
Summary
Diabetes is known to increase the risk of dementia. Although the mechanisms are currently unknown, a recently emerging body of evidence suggest that damaged blood vessels of the brain may be central to onset and progress of cognitive dysfunction. Consistently, the dysfunction of brain blood vessels is often observed in the brain of diabetes subjects. Therefore, this project will investigate whether the amelioration of disrupted brain blood vessels restores the cognitive function in diabetes.
Dementia Associated To Diabetes: Prevention Through The Modulation Of Cerebrovascular Integrity
Funder
National Health and Medical Research Council
Funding Amount
$719,770.00
Summary
Diabetic insulin resistance is reported to induce cognitive decline and dementia. An accumulating body of evidence suggest that compromised integrity of neurovascular unit and following changes in cerebral lipid homeostasis may be centrally involved in the neurodegeneration and cognitive deficits. Therefore, the project aims to prevent the insulin resistance-associated cognitive impairment by modulating the integrity of cerebrovasculature and lipid homeostasis.
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.
Predicting Renal, Ophthalmic And Heart Events In The Aboriginal Community: The PROPHECY Diabetes Multi-Omics Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$3,955,505.00
Summary
Diabetes is at epidemic levels in Indigenous Australians, impairing quality of life, and contributing to poor health. This is a result of rapid development of kidney, heart and eye complications. We have established a large long-term population study among Aboriginal communities within South Australia and will explore the burden, natural history and the social, psychological, environmental, clinical and genomic predictors of diabetes and its complications.
A Multi-setting Intervention To Reduce Sedentary Behaviour, Promote Physical Activity And Improve Childrens Health
Funder
National Health and Medical Research Council
Funding Amount
$860,343.00
Summary
Sedentary behaviours and physical inactivity play a major role in the rising prevalence of obesity among children in Australia. This intervention study will take place in the school and family settings which play a critical role in shaping children's health behaviours. The objective is to determine whether a 2-year behavioural intervention reduces sedentary behaviour and promotes physical activity and results in improved health among 8-9 year old children.