SRY protein explains why men more likely to develop Parkinson's

Feb 24 2006

Scientists at Prince Henry's Institute, Melbourne, and the University of California, Los Angeles, have discovered that SRY, the male protein that forms the testes is also produced in the brain region affected in Parkinson's disease. This discovery may explain why men are more likely than women to develop this degenerative disorder.

"Our research has shown that a gene only present in males contributes to the control of physical movement, a fundamental brain function," said Associate Professor Vincent Harley, Head of the Human Molecular Genetics Group at Prince Henry's Institute.

Parkinson's disease is a chronic movement disorder that affects an estimated 40,000 Australians. Men are 1.5 times more likely to develop the disease than women.

SRY, the protein that determines male gender, was discovered by British scientists in 1990. Dr Harley joined the team and was the first to show functions of the SRY protein in males. SRY is passed from father to son on the Y chromosome and is not present in females.

Co-investigators Dr Eric Vilain of UCLA and Dr Harley have now traced the SRY protein to a region of the brain called the substantia nigra, which deteriorates in Parkinson's disease.

Parkinson's disease develops when cells in the substantia nigra begin to malfunction and die, producing less dopamine. Dopamine, a chemical messenger, communicates with the brain to control movement and co-ordination. People with Parkinson's disease become unable to initiate or control their physical movements, eventually leading to paralysis.

The Prince Henry's Institute team, led by Dr Harley, developed sensitive new tools to detect SRY protein in the brain. UCLA scientists, led by Dr Vilain, lowered the level of SRY in the substantia nigra in animal models and detected a corresponding drop in tyrosine hydroxylase, which plays a key role in the brain's production of dopamine. The consequent low dopamine levels resulted in Parkinson's-like movement problems.

Drs Vilain and Harley believe that the variations in genes that control SRY or in the SRY gene itself may be linked to the onset of Parkinson's disease. Men with low levels of SRY may be at greater risk of developing the disease.

"We were surprised to find a function for SRY outside the testes," said Dr Harley.

Scientists at Prince Henry's Institute are collaborating with Associate Professor Catriona McLean, Director of the National Neural Tissue Resource Centre at the Alfred Hospital, Melbourne, to investigate SRY levels in the brains of males with Parkinson's disease.

Drs Harley and Vilain suspect that the normal role of SRY in the male brain could be to provide a protective effect against Parkinson's disease.

"The SRY gene may also explain the sex differences in other dopamine-linked disorders with a higher incidence in males, such as schizophrenia or addiction," said Dr Vilain.

One in seven people with Parkinson's disease are diagnosed before the age of 50 years, and the prevalence increases with age. Parkinson's disease worsens over time, and there is no known cause or cure. The severity and progression of the disease can vary greatly. Symptoms can be managed with medication and surgery.