Inclusion Body Proteins And Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$389,164.00
Summary
Parkinson's disease affects 1% of people aged over 50, and a related disorder, Dementia with Lewy bodies, causes dementia in elderly patients. These diseases are characterised by inclusion bodies (Lewy bodies) in a sub population of nerve cells. Multiple system atrophy, another adult-onset neurodegenerative disorder, is also characterised by inclusion bodies (glial inclusions). Inclusions may interfere with cellular function, contributing to the process of brain degeneration. The inclusion bodie ....Parkinson's disease affects 1% of people aged over 50, and a related disorder, Dementia with Lewy bodies, causes dementia in elderly patients. These diseases are characterised by inclusion bodies (Lewy bodies) in a sub population of nerve cells. Multiple system atrophy, another adult-onset neurodegenerative disorder, is also characterised by inclusion bodies (glial inclusions). Inclusions may interfere with cellular function, contributing to the process of brain degeneration. The inclusion bodies are precipitations of proteins and other cellular chemicals. In the last 10 years, in a search for the underlying cause of these neurodegenerative disorders, there has been an intensive research effort to identify the proteins precipitated in the inclusion bodies. The present project adopts a new strategy and aims to identify the precipitated proteins in the inclusion bodies in brains of people dying with Parkinson's disease, Dementia with Lewy bodies and Multiple system atrophy. We intend to isolate the Lewy bodies and the glial inclusions from fresh brain tissue of patients dying with relevant diseases. Throughout the various steps in the isolation process, the location of the inclusion bodies will be checked with a special antibody to a particular protein (alpha synuclein) which we and others have already discovered to be present in all inclusion bodies. Proteins will then be identified using electrophoresis and amino acid sequencing. With the identification of these proteins, their role in neurodegeneration in these diseases can be examined using multiple biomedical approaches. These proteins will be important candidates for developing novel diagnostic reagents, screening for gene mutations in patients, or as the target of therapeutic intervention in these diseases.Read moreRead less
Blood Proteins For Early Discrimination Of DEmentias
Funder
National Health and Medical Research Council
Funding Amount
$498,412.00
Summary
bPRIDE aims to develop blood biomarkers for early and specific diagnosis of the main dementia types: Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, and use these to develop diagnostic tests.
Regulation Of PML By E6AP: Implications For Tumour Development.
Funder
National Health and Medical Research Council
Funding Amount
$537,829.00
Summary
PML is a vital tumour suppressor, but little is known about its regulation. We established that PML levels are affected by another cellular protein E6AP. This study will define the mechanism by which E6AP influences PML. Human cancers will be screened for the involvement of these proteins, to gain new insights into cancer onset. The intended practical outcome of these studies is to aid cancer diagnosis and provide new anti-cancer drugs.
Investigating Biometal Dyshomeostasis In Dementia With Lewy Bodies
Funder
National Health and Medical Research Council
Funding Amount
$554,644.00
Summary
Dementia with Lewy bodies (DLB) is the second most common form of dementia after Alzheimer's disease (AD). Very little is known about what causes DLB and there are currently no effective therapeutics. An imbalance in naturally occurring biological metals such as iron and copper have been implicated in AD and Parkinson’s disease so this project will investigate if metals are involved in DLB. The ultimate goal of this project is to identify if metals are a valid target for future drug development.
Lewy Bodies In Patients With Dementia – Determining Common And Unique Mechanisms In Relation To Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$604,644.00
Summary
Alzheimer’s disease is the most common type of dementia but often has multiple mixed pathologies. For example, Alzheimer post mortem brains may have abnormal accumulation of Lewy bodies in certain parts of the brains, and could be diagnosed as Lewy body disease. This may represent a skewed representation of some dementia subtypes. This project will identify the biological determinants of dementia patients with Lewy body disease for better understanding and future therapeutic targeting.
Non-Alzheimer’s Disease Degenerative Dementias: Identifying Prodromal Genetic/familial Phenotypes, Modifying Factors, And Protein Variations Involved In Progression
Funder
National Health and Medical Research Council
Funding Amount
$6,449,246.00
Summary
This proposal will generate new knowledge necessary for advancing the diagnosis of the non-Alzheimer’s disease dementias. We will identify the preclinical forms of frontotemporal dementia and Lewy body dementia using similar methods to those successfully employed to advance diagnosis of Alzheimer’s disease. Importantly, our team has the capacity to translate these protocols into clinical practice and into further advances in biological knowledge that is necessary for future therapeutic targeting