Development Of Small Molecule IRAP Inhibitors For Treating Memory Deficits
Funder
National Health and Medical Research Council
Funding Amount
$369,898.00
Summary
We have identified a series of small molecule compounds based on their ability to inhibit the catalytic activity of a protein, IRAP using a computer model of IRAP to screen chemical libraries. This research proposal aims to investigate the properties of these compounds and their ability to treat Alzheimer's dementia. At the conclusion of this project, we will have 2 families of lead compounds suitable for development into a new class of therapeutic agents for treating Alzheimer's disease.
Development Of Small Molecule Inhibitors Of IRAP - Potential Use For The Treatment Of Memory Disorders
Funder
National Health and Medical Research Council
Funding Amount
$195,450.00
Summary
This research project provides proof of concept that IRAP is a suitable target for use in the development of a new class of clinically valuable cognitive-enhancing agents. We have recently Identified a family of small molecule compounds that inhibited the catalytic activity of the enzyme using a molecule model of IRAP to screen virtual libraries. This research proposal aims to validate that this family of compounds have memory-enhancing properties by acting specifically on IRAP. At the conclusio ....This research project provides proof of concept that IRAP is a suitable target for use in the development of a new class of clinically valuable cognitive-enhancing agents. We have recently Identified a family of small molecule compounds that inhibited the catalytic activity of the enzyme using a molecule model of IRAP to screen virtual libraries. This research proposal aims to validate that this family of compounds have memory-enhancing properties by acting specifically on IRAP. At the conclusion of this project, we will have elucidated important information on the specificity of the memory effects and the structure activity relationship of this family of compounds. We will have identified and characterised a lead compound for development into a new class of cognitive enhancers.Read moreRead less
Neural Correlates Of Fear Conditioning And Extinction
Funder
National Health and Medical Research Council
Funding Amount
$901,899.00
Summary
The amygdala is a part of the brain that processes emotional information. Disorders of amygdala function lead to a host of anxiety-related disorders such as phobias and post-traumatic stress disorder. In this grant we will study how the amygdala processes sensory information from the environment and forms memories of salient events. These findings will tell us how memories are formed, stored and retrieved. In the long term it will provide targets for the development of new anxiolytic agents
Targeting G-quadruplex DNA As A Novel Therapeutic Strategy For Alzheimer’s And Frontotemporal Dementia
Funder
National Health and Medical Research Council
Funding Amount
$720,144.00
Summary
Dementia is the third leading cause of death in Australia and there is an urgent need to identify new ways of treating diseases that cause dementia. Our research is focused on targeting an unusual DNA structure in Alzheimer’s and Frontotemporal dementia (FTD). We will use a precision-targeted technology to better control formation of this DNA structure in disease-causing genes, allowing us to switch off the gene and hence stop disease progression for Alzheimer’s and FTD.
BDNF Genotype And Emotional Memory In Post-traumatic Stress Disorder
Funder
National Health and Medical Research Council
Funding Amount
$108,902.00
Summary
This project addresses the question of why some people develop PTSD following trauma and others don’t. It will assess the influence of genetics (specifically a genotype that influences Brain Derived Neurotrophic Factor) on emotional memory processes as distressing emotional memories are a core symptom of PTSD. If we find that people with a particular genetic profile have a greater risk of developing intrusive memories after trauma, this will help us better target treatment for those individuals.
A Randomised Controlled Trial Of Physical Activity With Individual Goal-setting And Volunteer Mentors To Overcome Sedentary Lifestyle In Older Adults At Risk Of Cognitive Decline
Funder
National Health and Medical Research Council
Funding Amount
$506,405.00
Summary
Thirteen percent of all cases with Alzheimer’s Disease are potentially due to a lack of physical activity. This study investigates whether a 6-month physical activity program can significantly increase physical activity levels in older adults who are concerned about their memory and who are not physical active. New about this trial is that participants can choose their own goals they want to reach and the additional involvement of physical active volunteers who will support the participants.
Gene-environment Interactions Modulating Cognition And Dementia In Huntington’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$394,425.00
Summary
We are investigating mechanisms whereby cognitive symptoms, culminating in dementia, occur in a fatal brain disease, Huntington’s. We will explore how the ‘genetic stutter’ affects the brain at the level of molecules and cells, which will help identify targets for future treatment. We will also establish how environmental factors, including cognitive stimulation, physical activity and stress, modulate dementia. This will inform the development of treatments for this currently incurable disease.
Clinical And Biological Markers Of Disease Presentation And Progression In Early Frontotemporal Dementia
Funder
National Health and Medical Research Council
Funding Amount
$507,636.00
Summary
Frontotemporal dementia accounts for 12-20% of all dementia cases and is as common as Alzheimer's disease in the < 65 year olds. Our understanding of this disease remains limited. This project aims to better characterise the range and progression of deficits in early frontotemporal dementia using tests of brain function and magnetic resonance imaging. This will assist in better diagnosis of these patients and, ultimately, may be used to monitor the outcomes of therapeutic interventions.
Improving Clinical Diagnosis Of Mild Neurocogntive Disorders Using Neuropsychological Assessment
Funder
National Health and Medical Research Council
Funding Amount
$155,932.00
Summary
A major proportion of neuropsychiatric disability in old age is due to dementia or milder cognitive disorders. However, these disorders can be challenging to diagnose because of the subtlety of cognitive deficits and a lack of appropriate normative reference groups. By developing comprehensive, representative Australian normative data for key diagnostic measures and refining clinical diagnostic methods, the study will have a major impact on the accuracy of neuropsychological assessment practice.
Huntington’s disease (HD) is a devastating neurodegenerative disorder which shares several features with Alzheimer’s and Parkinson’s disease (i.e. dementia-like cognitive deficits). There is currently no cure for HD. Using a mouse model of HD and a combination of relevant drugs (i.e. N-Acetylcysteine and deferiprone) targeting two distinct levels of the cascade of events leading to HD, we will slow down the progression of the disease and correct dysfunctions within the brain.