Parkinson’s disease is the second most common neurodegenerative disorder, with 6.3 million people diagnosed worldwide; 80,000 of these are Australian. This means that around one out of every 350 Australians suffers from this life changing debilitating disease. Parkinson’s disease appears more frequently in males than females. The majority of Parkinson’s disease cases are idiopathic- of unknown cause.   Parkinson’s disease is characterised by degeneration in the dopaminergic neurons in the substantia nigra (a structure in the midbrain).  The dopaminergic neurons are nerve cells that make and contain a neurotransmitter known as dopamine. Oxidative stress and neuroinflammation are thought to be involved in degeneration of the dopaminergic neurons.   

The researchers have some exciting data. Many enzymes are activated when they become phosphorylated. Tyrosine hydroxylase is the enzyme which converts the amino acid tyrosine to L-DOPA, the precursor of dopamine. They injected low levels of a bacterial molecule (LPS) into young models and found an increase in the phosphorylation and activity of tyrosine hydroxylase in the adrenal gland of these models. The researchers found that this activation was sustained throughout adolescence and adulthood. Interestingly, LPS produced a sustained increase in the activation of tyrosine hydroxylase in male model but not in female. The researchers then went on to show a very significant increase in tyrosine hydroxylase phosphorylation and activation in tissues from patients with Parkinson’s disease. This means that this enzyme is active and making a lot of dopamine in people with Parkinson’s disease.  Dopamine can break down into very toxic substances and could be causing the damage to neurons seen in Parkinson’s disease.

The aim of this research project is to determine if bacterial infection could be causing an increase in the activation of tyrosine hydroxylase in patients with Parkinson’s disease.

The researchers will:

1) Investigate the effect of bacterial infection (using the LPS molecule) on the regulation of dopamine synthesis in different brain regions.

2)  Investigate the effect of bacterial infection on the activation of microglia (immune defence cells) in the different regions of the brain.

3) Investigate whether oxidative stress due to an up-regulation of dopamine synthesis and neuroinflammation can cause the delayed, progressive and selective loss of dopaminergic neurons in the mid brain.

This team of researchers are the world leaders in understanding the mechanisms that control dopamine synthesis. This work provides for the first time a key link between bacterial infection and the degeneration of neurons seen in Parkinson’s disease, providing a new way of unlocking the cause of Parkinson’s disease.

Researchers 

Associate Professor Phillip Dickson, Emeritus Professor Peter Dunkley, Lin Kooi Ong

Research Area 
Project type 
Project Grant
Year of funding 
2014