Investigating The Involvement Of Human Derived Astrocytes And Motor Neurons In The Pathology Of Motor Neuron Disease.
Funder
National Health and Medical Research Council
Funding Amount
$287,321.00
Summary
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease, which results in the death of nerves that innervate muscle, known as motor neurons. Recent studies using mouse ALS models showed that certain cells that normally support motor neurons may be directly contributing to their death in ALS. We propose to derive ALS-diseased human cells and investigate how these cells may react in ‘normal’ tissue. These studies are clinically relevant in understanding ALS pathological processes.
Motor Neurone Disease - Pathophysiological Insights Into The Site Of Origin And Patterns Of Neurodegeneration.
Funder
National Health and Medical Research Council
Funding Amount
$309,361.00
Summary
Motor neurone disease (MND) kills one Australian per day and is characterised by progressive loss of the corticospinal tract, that controls all voluntary movements. The present project will investigate where MND begins and document how the loss of nerves within the brain, spinal cord and peripheral nerves evolves. In addition to providing information about prognosis, new quantifiable measures will be developed to objectively monitor patients in future treatment and prevention trials.
The Role Of Oxidative Stress In The Patho-aetiology Of Prion Disorders Using Infected Cell Culture And Animal Models
Funder
National Health and Medical Research Council
Funding Amount
$112,014.00
Summary
The transmissible spongiform encephalopathies (TSE; also known as prion diseases) are a biologically unique and fascinating group of invariably fatal diseases which primarily affect the brains of both humans and animals. In humans, sporadic Creutzfeldt-Jakob disease (CJD) is the most common form, while in animals it is the recent epidemic of bovine spongiform encephalopathy (mad cow disease), and its probable transmission to humans as new variant CJD, which has drawn so much attention to this gr ....The transmissible spongiform encephalopathies (TSE; also known as prion diseases) are a biologically unique and fascinating group of invariably fatal diseases which primarily affect the brains of both humans and animals. In humans, sporadic Creutzfeldt-Jakob disease (CJD) is the most common form, while in animals it is the recent epidemic of bovine spongiform encephalopathy (mad cow disease), and its probable transmission to humans as new variant CJD, which has drawn so much attention to this group of disorders. The preponderance of scientific evidence now supports the belief that infectivity in TSEs relates predominantly (probably exclusively) to a protein (called the prion protein; PrP) which is normally found on the cell surface of a number of types of brain cells, including neurons. Transmissibility, and hence infectivity, is more correctly associated with a malfolded version of PrP into an abnormal shape which gives the mutant protein significantly different biological and biochemical properties, including relative resistance to breakdown by enzymes that metabolise proteins (proteases) and enhanced tendency to aggregate. However, the precise steps involved in this transformation to the abnormal infectious form of PrP are not known. Similarly, our understanding of how different folding and accumulation of this protein brings about disease is not clear. Nevertheless, as with other neurological diseases (eg Alzheimer's disease) which are a consequence of unexplained spontaneous premature degeneration of parts of the brain (neurodegenerative diseases), oxidative stress is increasingly believed to play a role. Oxidative stress is a generic term used to describe the enhanced production within a cell of small, very harmful, oxygen containing molecules which under normal circumstances can be successfully detoxified. This project involves a detailed study of the role of oxidative stress in the causation of prion diseases using both mouse and cell culture models.Read moreRead less
Aberrant Oligosaccharide Processing Of Nox2-oxidase As A Mechanism Of Vascular Oxidative Stress In Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$552,565.00
Summary
Excessive production of free radicals by an enzyme called Nox2 may be a cause of artery disease leading to heart attacks and strokes. This study will identify whether the addition of sugarchains to Nox2 causes it to be expressed at the surface of cells allowing the free radicals it produces to exit the cell and cause damage to the blood vessel wall. Charaterising this new pathway of excessive free radical production may pave the way for new diagnostics and treatments for artery disease.