Brain Metal Neurochemistry: Mechanism-driven Drug Discovery For Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
Alzheimer’s disease (AD) is a complex disease where certain proteins congeal in the brain and metals accumulate. This project investigates the function of the proteins in microscopically transporting the metals. It will also look for tests that predict the onset of AD by measuring iron and iron related proteins by using special brain imaging (MRI), and measurements in spinal fluid. Finally, it will test drug candidates that target the metals, in animal models of AD, and in early clinical trials.
Anti-inflammatory Copper Complexes For Treatment Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$603,622.00
Summary
Brain inflammation and disrupted metabolism of the biologically important metal, copper, play key roles in Alzheimer’s disease (AD) progression. Our team has developed new copper-based therapeutics, but limited knowledge of how they work impedes clinical trials. My recent findings indicate that these drugs potently prevent inflammation. My proposal seeks to understand how copper-complexes reduce damaging inflammatory responses in novel human cell models of AD.
The Molecular Basis For Manganese Uptake By Pathogenic Bacteria.
Funder
National Health and Medical Research Council
Funding Amount
$632,949.00
Summary
Bacterial antimicrobial resistance is an increasing threat to human health. At this point in time, there is an urgent, fundamental need for the development of new antimicrobial strategies. Bacterial infection involves a constant tug-of-war between the pathogen and the human host for the essential nutrients of life, including trace metal nutrients such as Mn. This project seeks to understand the machinery for Mn uptake by pathogenic bacteria as a target for novel antibacterial design.
Modulation Of Neurotherapeutic Cell Signalling Pathways By Metallo-complexes As A Treatment For Alzheimers Disease.
Funder
National Health and Medical Research Council
Funding Amount
$653,113.00
Summary
Alzheimer's disease (AD) is an enormous burden on the Australian health care system . We have begun to investigate therapeutic treatments based on triggering protective cell signalling pathways with metal-based compounds. These compounds trigger the activation of a signalling cascade resulting in inhibition of AD-associated symptoms. In this proposal we will further investigate how these compounds modulate specific receptors and cellular kinase activity to protect neurons in the AD brain.
NOVEL THERAPIES FOR ALZHEIMER'S DISEASE BASED ON A-BETA - METAL INTERACTIONS
Funder
National Health and Medical Research Council
Funding Amount
$461,443.00
Summary
The genetic data clearly show that the amyloid protein (A-beta) is central to the brain damage which occurs in Alzheimer's disease (AD). However exogenous or environmental factors involved in regulating its toxic actions are not understood. We have shown that the metals zinc and copper have dramatic effects on the properties of A-beta and that chemicals which alter the amounts of these metals in the brain may be useful in treating the disease. In this project we are investigating the ability of ....The genetic data clearly show that the amyloid protein (A-beta) is central to the brain damage which occurs in Alzheimer's disease (AD). However exogenous or environmental factors involved in regulating its toxic actions are not understood. We have shown that the metals zinc and copper have dramatic effects on the properties of A-beta and that chemicals which alter the amounts of these metals in the brain may be useful in treating the disease. In this project we are investigating the ability of one such compound to affect the metabolism of A-beta in a mouse model of AD.Read moreRead less
I am a molecular and cellular biologist determining the molecular mechanisms responsible for the neurodegeneration in Alzheimer’s, Parkinson’s and Prion disease.
Mechanism Of Action Of A Quinazolinone In Models Of PD
Funder
National Health and Medical Research Council
Funding Amount
$667,548.00
Summary
By the time symptoms of Parkinson's disease (PD) appear, 60-70% of the cells in a crucial part of the brain called the substantia nigra have been destroyed and within a few years of diagnosis, most of the remaining cells have died. This project investigates the causes of this cell loss and a how a new class of compounds could interrupts the process. Success in achieving the aims of this proposal will add to our knowledge of the causes of neuronal death in PD
Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Resistance by cancers to established chemotherapeutics is a growing problem in the community and one that demands the development of new strategies. Chelators that target the essential element iron within cancer cells represent a novel and promising approach to this problem. The Chief Investigators represent a unique combination of expertise in coordination chemistry and the biochemistry of iron chelati ....Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Resistance by cancers to established chemotherapeutics is a growing problem in the community and one that demands the development of new strategies. Chelators that target the essential element iron within cancer cells represent a novel and promising approach to this problem. The Chief Investigators represent a unique combination of expertise in coordination chemistry and the biochemistry of iron chelation. They have discovered and characterised new chelators that show marked anticancer activity, and act by a new mechanism that overcomes problems of resistance. In this project they will pursue a course that will lead to a greater understanding of how these compounds work with the outcome that new effective anticancer drugs may emerge.Read moreRead less
I am a pharmacologist-cell biologist-molecular biologist and chemist examining the metabolism of iron in normal and neoplastic cells and the development of iron chelators for the treatment of a wide variety of diseases eg., ?-thalassaemia, cancer and Frie
The Modulation Of Metals To Improve The Cognitive And Pathological Features Of Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$436,238.00
Summary
This proposal will characterise the effects of a novel therapy for the treatment of Alzheimer's disease. Our preliminary data show that this approach can affect both the onset and progression of the disease, as well as the symptoms that characterise it. Thus, a thorough assessment of these effects and this drug target provides a tangible movement towards a truly effective treatment for Alzheimer's disease.