Molecular Mechanism And Therapeutic Implications Of Prion Disease Strain Types In Sporadic Creutzfeldt Jakob Disease.
Funder
National Health and Medical Research Council
Funding Amount
$345,634.00
Summary
The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms also exist. Prion diseases are transmissible by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been conclusively identified. However, a major component of purified prions is an ....The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms also exist. Prion diseases are transmissible by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been conclusively identified. However, a major component of purified prions is an abnormal disease associated form of the host prion protein. Differences in the duration of illness and pathology of sporadic CJD suggests that the disease may be caused by different prion strains. The existence of different prion strains may explain the limited clinical success of anti-prion therapeutics modeled in rodent models of prion diseases. In this study a cell-free model of prion propagation will be used to investigate the basis of human prion strains. This assay will also be used to identify and determine whether the therapeutic efficacy of anti-prion compounds is influenced by human prion strain type. This study will represent the first host species and prion strain specific screen of anti-prion therapeutics aimed at developing the best possible model for the identification and development of therapeutics for human prion diseases.Read moreRead less
How Do Small Extracellular Vesicles Contribute To The Development Of Prion Disease
Funder
National Health and Medical Research Council
Funding Amount
$563,897.00
Summary
Prion diseases are transmissible neurodegenerative disorders associated with the misfolding of the prion protein. This proposal will investigate how cells release the infectious agent responsible for prion diseases in small nanovesicles known as exosomes. We will characterise the novel processed forms of the proteins involved in these two neurodegenerative diseases within the exosomes and investigate whether the genetic content of exosomes has diagnostic potential.
Tackling Key Epidemiological And Basic Scientific Research Issues In Prion Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$401,109.00
Summary
Proposed Practitioner Fellowship research will simultaneously include epidemiological and basic scientific projects, emphasising human prion disease. Epidemiological research will involve large-scale studies to clarify genetic factors that influence susceptibility to developing prion disease, as well as clarify whether Alzheimer disease is transmissible, while basic scientific research will include determining the characteristics of the misfolded prion proteins causing neuronal disease.
Investigating The Biological Significance Of Proteolytic Prion Protein Processing.
Funder
National Health and Medical Research Council
Funding Amount
$328,558.00
Summary
Prion diseases, including Bovine Spongiform encephalopathy (“mad cow disease”) and Creutzfeldt-Jakob Disease in humans are transmissible and fatal diseases that occur when the normal prion protein (PrPc) mis-folds and accumulates in the brain. The specific function of PrPc within a cell remains unclear, however its presence is essential for prion diseases to occur. This project aims to define how PrPc cleavage affects its biological function(s), and influences susceptibility to prion infection.
Cellular Pathogenesis Of Key Proteins Involved In Neurodegenerative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$312,730.00
Summary
Prion proteins are involved in neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) and Bovine Spongiform Encephalopathy (BSE). The aim of this research proposal is to investigate factors which can change the prion protein from a normal, benign, form into an abnormal shape which can cause disease. The outcomes of this work will provide further insight into the role of prion proteins in these diseases and also for other neurodegenerative disorders such as Alzheimer's disease.
Prion-like Behaviour In Immunity: Super-sized Signalling Platforms?
Funder
National Health and Medical Research Council
Funding Amount
$611,995.00
Summary
Prions have been mostly associated with pathologies but recent discoveries show that prion-like behaviour may be beneficial, enhancing our immune response for example. To test this, we want to systematically explore all human proteins involved in the defence against pathogens, find new prion-like trends and probe their role in the innate immune response.
How Do Glycosaminoglycans Promote The Propagation Of Prions?
Funder
National Health and Medical Research Council
Funding Amount
$512,270.00
Summary
The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms are recognised. Prion diseases are transmissible to the same species by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been identified at the molecular level. However, a major c ....The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms are recognised. Prion diseases are transmissible to the same species by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been identified at the molecular level. However, a major component of purified prions is an abnormal disease associated form of the host encoded prion protein. Understanding how the disease associated form of the prion protein is generated and how host-derived cofactors contribute to its formation will help in our understanding of the infectious nature of these diseases and in the development of effective therapeutic and prophylactic strategies. Glycosaminoglycans are host-derived components of the extracellular matrix that are associated with prion protein plaques found in the brain tissue of patients with prion diseases. Glycosaminoglycans are believed to influence the transmission of prions and the ongoing propagation of infectivity. In this study the importance of glycosaminoglycans in the formation of the disease associated prion protein and the generation of infectivity will be investigated using both cell-free and cell-based models of prion propagation. The understanding gained from this study will be used to develop a high throughput assay that can be used to detect prion infection prior to the development of clinical disease and within a time frame whereby therapeutic intervention may be effective.Read moreRead less
Nerodegeneration In The Aging Brain: How The Pathways Leading To Aggregating Protein Cause Disease
Funder
National Health and Medical Research Council
Funding Amount
$15,050,508.00
Summary
The Neurodegeneration Program is discovering the basic pathways that cause Alzheimer’s disease and related diseases of the aging brain; from these discoveries the team are finding new methods for early diagnosis and therapeutic interventions which will allow them to determine whether it is possible to delay the onset or improve the way in which the brain copes with these diseases
Cellular Pathogenesis Of Neurodegenerative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$124,530.00
Summary
Alzheimer's disease is the most common neurodegenerative disease of the ageing population and is associated with toxicity of the Abeta peptide. Prion diseases (eg CJD in humans) are infectious neurodegenerative disorders caused by misfolding of the prion protein. This proposal aims to bring together similar features of these diseases using novel cell and animal based studies to develop better diagnostics and greater understanding of the molecular basis of these disorders with a view to developin ....Alzheimer's disease is the most common neurodegenerative disease of the ageing population and is associated with toxicity of the Abeta peptide. Prion diseases (eg CJD in humans) are infectious neurodegenerative disorders caused by misfolding of the prion protein. This proposal aims to bring together similar features of these diseases using novel cell and animal based studies to develop better diagnostics and greater understanding of the molecular basis of these disorders with a view to developing interventional therapies.Read moreRead less