Cognition In Cerebellar Degeneration: Correlations With Lateral Neocerebellar Dysfunction And Atrophy
Funder
National Health and Medical Research Council
Funding Amount
$205,500.00
Summary
Diseases of the main brain coordination centre (the cerebellum) were once thought to impair only movement skills. However, effects on thinking, and especially on mental flexibility and rational planning, are increasingly being reported. These cognitive difficulties may hinder rehabilitation. They also often cause tension within the sufferers' families if other family members are not aware that such difficulties are part of the disease and beyond the sufferers' control. We will test how common su ....Diseases of the main brain coordination centre (the cerebellum) were once thought to impair only movement skills. However, effects on thinking, and especially on mental flexibility and rational planning, are increasingly being reported. These cognitive difficulties may hinder rehabilitation. They also often cause tension within the sufferers' families if other family members are not aware that such difficulties are part of the disease and beyond the sufferers' control. We will test how common such thinking difficulties are in patients with different inherited forms of incoordination, and determine what aspects of thinking are particularly affected. We will see whether the severity of movement incoordination predicts the extent of thinking disruption, as different but neighbouring parts of the cerebellum seem to be involved in each. We will also use magnetic brain scans (MRI's) to check that the thinking problems are not caused by shrinkage of other parts of the brain in these diseases.Read moreRead less
The Role Of Dysferlin In Muscular Dystrophy And Skeletal Muscle Membrane Repair.
Funder
National Health and Medical Research Council
Funding Amount
$316,667.00
Summary
Patients who lack the protein dysferlin have muscular dystrophy. These patients are unable to repair their muscle membranes, which get damaged during normal activities. A defect in membrane repair is a new pathway implicated in the muscular dystrophies, and it is likely that other patients will also have defective muscle membrane repair. We will find out how dysferlin mediates its role in membrane repair, and identify other dysferlin-interacting proteins, as these may also underlie disease.
Development Of A New Method Of Motor Unit Number Estimation For Use In Motor Neurone Disease
Funder
National Health and Medical Research Council
Funding Amount
$480,127.00
Summary
This project aims to help understand motor neurone disease, which is a severe disease that leads to paralysis and death. In motor neurone disease there is of death of the nerve cells that maks muscles move. We have developed a new method of measuring the number of motor nerve cells. We will use this to study the different types of motor neurone disease.
Alpha-synuclein Metabolism In Human Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$381,430.00
Summary
Alpha-synuclein is an abundant brain protein of unknown function. Gene mutations have been linked to rare cases with inherited Parkinson s disease. Now this protein is believed to play an important role in all forms of Parkinson s disease, Lewy body dementia, and multiple system atrophy. These diseases are designated as synucleinopathies to emphasize the potential importance of alpha-synuclein in these disease. Recent studies suggest alpha-synuclein may also contribute to many other human diseas ....Alpha-synuclein is an abundant brain protein of unknown function. Gene mutations have been linked to rare cases with inherited Parkinson s disease. Now this protein is believed to play an important role in all forms of Parkinson s disease, Lewy body dementia, and multiple system atrophy. These diseases are designated as synucleinopathies to emphasize the potential importance of alpha-synuclein in these disease. Recent studies suggest alpha-synuclein may also contribute to many other human diseases, including Alzheimer s disease. The reason how and why alpha-synuclein is involved in so many human neurological diseases is not clear. We recently discovered that alpha-synuclein in normal human brain exists in multiple form of N-terminal fragments, presumably generated through certain endogenous enzymes. These cleaved products are markedly increased in Parkinson s disease. Studies by other groups suggest alpha-synuclein and fragments may be released to the cerebrospinal fluids. Based on these findings, we hypothesize that alpha-synuclein is modified by specific enzymes in neurons and released. This is probably a normal alpha-synuclein metabolic pathway whose homeostasis may be, for reasons yet to be understood, altered in synucleinopathies. Similar mechanism may be also involved in other common diseases in which the protein is believed to play a role. This project aims to elucidate the potential role of alpha-synuclein metabolism in Parkinson s and related diseases by examining alpha-synuclein metabolites in the brains affected by these diseases. Results from this grant will provide new information about alpha-synuclein metabolism in neurons, new insights into the mechanistic involvement of alpha-synuclein in these neurodegenerative diseases. Antibody reagents generated from this study may be valuable in neuropathological and clinical assessment of changes in synucleinopathies.Read moreRead less
Targeting Beta-adrenergic Signalling To Improve Muscle Regeneration In Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$473,224.00
Summary
Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy, caused by a lack of a protein called dystrophin. Dystrophic muscles are fragile, prone to injury, and have a compromised ability to regenerate after damage. Modulating pathways regulating beta-adrenergic signalling has potential to attenuate the dystrophic pathology and to delay the onset or slow the progression of the muscle wasting and weakness in muscular dystrophy.
Excitation-contraction Coupling In Skeletal Muscle In Health, Exercise And Disease
Funder
National Health and Medical Research Council
Funding Amount
$623,621.00
Summary
Skeletal muscle dysfunction occurs in certain diseases, aging and exercise, and can deleteriously affect lifestyle and mobility. This project investigates the molecular mechanisms involved in the complex sequence of events that occur in each individual muscle fibre, starting from stimulation by a nerve through to the fibre contracting. This should give information about causes of skeletal muscle dysfunction in myotonia, heart failure and other situations, and help development of therapies.