How Does Iron Accumulation Affect Parkinson’s Disease And What Controls It?
Funder
National Health and Medical Research Council
Funding Amount
$545,517.00
Summary
Currently there is no cure for Parkinson's disease, and although we have a number of treatments to manage the disease there is an urgent need for a further understanding of the disease process. This proposal will investigate the critical role that iron plays in the cause of neuronal cell death that results in Parkinson's disease, and will investigate methods for regulating metal levels in the brain.
Neuronal Membranes And Connections In Dementia: Targets For Intervention
Funder
National Health and Medical Research Council
Funding Amount
$720,144.00
Summary
This research aims to understand why some people with Mild Cognitive Impairment (MCI) progress to dementia, whilst others do not. The fact that some people’s cognitive abilities can improve provides an opportunity to study the mechanisms that protect their brain cells from the degeneration associated with dementia. Understanding the cellular changes will lead to therapies that can be tested in the lab for individuals.
Functional Maturation Of Adult Neural Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$701,390.00
Summary
This proposal seeks to understand how the production of functional nerve cells in the brain is regulated. Specifically we will focus on the way in which adult neuronal precursor cells (neuroblasts) in the brain acquire their functional characteristics as they mature into active entities capable of forming neural networks. We will examine the expression and activation of specific membrane proteins (ion channels) on the differentiation and migration of neuronal precursor cells.
Identifying Genetic Pathways Underlying The Development Of Distinct Neuronal Subtypes Among Midbrain Dopamine Neurons.
Funder
National Health and Medical Research Council
Funding Amount
$462,709.00
Summary
There is an urgent need in the field of Parkinson's disease (PD) research to develop new strategies aimed at halting progression of the disease (neuroprotection) and alleviaing the symptoms (restorative therapy). This project employs a novel and innovative design to identify genes expressed specifically by the cell type most effected in PD and therefore provide new genetic targets for neuroprotective and resorative therapy.
Cellular And Molecular Mechanisms Of Development And Regeneration In The Olfactory System
Funder
National Health and Medical Research Council
Funding Amount
$345,773.00
Summary
During development of the fetal brain, cells are wired together. The correct wiring patterns are essential for normal function of the brain. Growth and formation of new connections decreases after birth. For this reason, the repair of the damaged adult nervous system is limited. However, there is one region in the nervous system that exhibits continual growth and repair throughout life. This is the nerve that is responsible for smell and connects the nose to the brain. The aim of this study is t ....During development of the fetal brain, cells are wired together. The correct wiring patterns are essential for normal function of the brain. Growth and formation of new connections decreases after birth. For this reason, the repair of the damaged adult nervous system is limited. However, there is one region in the nervous system that exhibits continual growth and repair throughout life. This is the nerve that is responsible for smell and connects the nose to the brain. The aim of this study is to identify the processes that permit continual growth within this region of the nervous system.Read moreRead less
Creating Stem Cell Niches To Repair The Nigrostriatal System
Funder
National Health and Medical Research Council
Funding Amount
$837,033.00
Summary
It has been difficult to treat Parkinson's with stem cells because transplants make to few new cells and form tumors. In other organs, specialized locations called niches regulate the division and maturation of stem cells. By making a niche in the brains of animals with experimental parkinsonism we induced the brain to make new nerve cells and repair the parkinsonism. This is important because it shows how to use cell based therapies to treat neurodegenerative disorders. .
Toward Cell-replacement Therapy For Parkinson's Disease: Investigating Endogenous Dopamine Neurogenesis In The Adult Mouse Substantia Nigra
Funder
National Health and Medical Research Council
Funding Amount
$577,957.00
Summary
Death of a particular type of cell in the brain causes the movement symptoms of Parkinson's disease (PD) (e.g. tremor). This study investigates how these cells are normally replaced, and whether stimulating their replacement can alleviate movement symptoms in an animal model of PD. Fulfillment of these aims will deliver vital information about how we might delay and better treat the movement symptoms of PD.
IS THERE A ROLE FOR ENDOPLASMIC RETICULUM STRESS IN THE PATHOGENESIS OF ALS?
Funder
National Health and Medical Research Council
Funding Amount
$535,710.00
Summary
Motor neuron disease (MND) is a devastating and rapidly progressing adult onset disease; most patients die 2-5 years after diagnosis. MND is characterized by the death of specific cells, called 'motor neurons' within the nervous system. Unfortunatley, MND currently has an unknown cause and no effective treatment. This proposal aims to study the mechanisms that trigger degeneration of motor neurons in MND. Some forms of MND are inherited and linked to mutations in a protein called SOD1, but how t ....Motor neuron disease (MND) is a devastating and rapidly progressing adult onset disease; most patients die 2-5 years after diagnosis. MND is characterized by the death of specific cells, called 'motor neurons' within the nervous system. Unfortunatley, MND currently has an unknown cause and no effective treatment. This proposal aims to study the mechanisms that trigger degeneration of motor neurons in MND. Some forms of MND are inherited and linked to mutations in a protein called SOD1, but how the mutations lead to cell death is unclear. However, SOD1 mutants are known to clump together in large aggregates and this is linked to toxicity. In a previous study, we found that normally SOD1 is secreted from the cell where it can protect the motor neuron from oxidative damage. However SOD1 mutants are not secreted as well as the normal protein, leaving the cell vulnerable to damage. In addition, the compartment of the cell responsible for secretion,the 'endoplasmic reticulum' (ER), is under stress due to secretory dysfunction of mutant SOD1. Our data suggest that this ER stress leads to the activation of 'cell suicide' pathways, leading to death of the motor neuron. However, very little is known about how molecular events in the ER lead to cell death in MND. This proposal will examine these processes in detail. In other studies, we found that a molecule called 'PDI' inhibits mutant SOD1 from aggregation and is made in large quantities in our laboratory models of MND. This proposal will determine if PDI is potentially a new therapeutic target for MND due its ability to protect the cell from the toxic effects of SOD1 aggregation. Our findings are both novel and exciting and propose previously unexplored mechanisms of disease and new theraputic targets. Once we understand the basic mechanisms occuring in the motor neuron, which we can design specific therapies to halt the progression of the disease and prolong the life of human MND patients.Read moreRead less
Studies On Induction Of Antigen Specific T Regulatory Cells To Control Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$353,033.00
Summary
The immune system has natural control mechanisms, called regulatory cells. Our group was the first in the world to correctly identify these cells. There is now a world-wide interest in these cells as they can prevent unwanted immune mediated injury. In autoimmune diseases such as multiple sclerosis, regulatory cells can prevent relapse and progression. This project will identify ways of producing potent specific regulatory cells to control multiple sclerosis and other debilitating neurological d ....The immune system has natural control mechanisms, called regulatory cells. Our group was the first in the world to correctly identify these cells. There is now a world-wide interest in these cells as they can prevent unwanted immune mediated injury. In autoimmune diseases such as multiple sclerosis, regulatory cells can prevent relapse and progression. This project will identify ways of producing potent specific regulatory cells to control multiple sclerosis and other debilitating neurological diseases.Read moreRead less