Journal of Biological Chemistry

Sudden decline in male testosterone may cause Parkinson’s disease.

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The results of a new study by neurological researchers at Rush University Medical Center show that a sudden decrease of testosterone, the male sex hormone, may cause Parkinson’s like symptoms in male mice. The findings were recently published in the Journal of Biological Chemistry.

One of the major roadblocks for discovering drugs against Parkinson’s disease is the unavailability of a reliable animal model for this disease.

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“While scientists use different toxins and a number of complex genetic approaches to model Parkinson’s disease in mice, we have found that the sudden drop in the levels of testosterone following castration is sufficient to cause persistent Parkinson’s like pathology and symptoms in male mice,” said Dr. Kalipada Pahan, lead author of the study and the Floyd A. Davis endowed professor of neurology at Rush. “We found that the supplementation of testosterone in the form of 5-alpha dihydrotestosterone (DHT) pellets reverses Parkinson’s pathology in male mice.”

“In men, testosterone levels are intimately coupled to many disease processes,” said Pahan. Typically, in healthy males, testosterone level is the maximum in the mid-30s, which then drop about one percent each year. However, testosterone levels may dip drastically due to stress or sudden turn of other life events, which may make somebody more vulnerable to Parkinson’s disease.

“Therefore, preservation of testosterone in males may be an important step to become resistant to Parkinson’s disease,” said Pahan.

Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of Parkinson’s disease. Nitric oxide is an important molecule for our brain and the body.

“However, when nitric oxide is produced within the brain in excess by a protein called inducible nitric oxide synthase, neurons start dying,” said Pahan.

“This study has become more fascinating than we thought,” said Pahan. “After castration, levels of inducible nitric oxide synthase (iNOS) and nitric oxide go up in the brain dramatically. Interestingly, castration does not cause Parkinson’s like symptoms in male mice deficient in iNOS gene, indicating that loss of testosterone causes symptoms via increased nitric oxide production.”

“Further research must be conducted to see how we could potentially target testosterone levels in human males in order to find a viable treatment,” said Pahan.S

Source: http://machineslikeus.com

 

Cancer cell enzymes shown to act as ‘good cops.

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Enzymes released by cancerous cells have a protective function and are not one of the “bad guys”, say researchers from the University of East Anglia.

Their study found the MMP-8 enzyme sent a signal to the immune system to attack the tumour.

Patients whose breast tumours have more of this enzyme seem to do better.

Cancer Research UK said the research provided “very early clues” as to how the enzyme might recruit cells to fight breast cancer.

Scientists from UEA worked with clinicians at the Norfolk and Norwich University Hospital to look in detail at the patterns of MMPs in breast tumours from patients.

Their study, published in the Journal of Biological Chemistry, reveals that the matrix metalloproteinase-8 enzyme (MMP-8) could be acting as the ‘good guy’ by alerting the immune system to the location of the tumour.

It had been thought that the production of MMPs by breast cancer cells helped to promote cancer growth.

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MMP-8 acts as a sort of ‘find me’ signal to the immune system, which then becomes activated to attack the tumour”

Prof Dylan Edwards, lead researcher from UEA’s School of Biological Sciences, said that if breast cancer cells produce MMP-8 it causes them to produce two other inflammatory factors (IL-6 and IL-8) that have previously been shown to promote cancer.

“They were once thought to act like ‘molecular scissors’ to snip away at the scaffolding structures outside cells and clear a path for the cancer cells to invade and spread to other organs.

“However, breast tumour cells that over-produce MMP-8 don’t survive long-term – the enzyme stops them growing,” he said.

“We now think that in tumours, MMP-8 acts as a sort of ‘find me’ signal to the immune system, which then becomes activated to attack the tumour, which may help to explain its protective function.”

Drugs used to treat cancer in the 1990s, which blocked these enzymes, failed in the clinic, he said, and this new research may explain why.

It is still not known exactly how MMP-8 causes IL-6 and IL-8 to be activated.

Finding this out will be an important step forward which will help direct further research.

Dr Emma Smith, senior science information officer at Cancer Research UK, said: “This study provides very early clues as to how the MMP-8 protein might actually play the role of a ‘good cop’ and recruit immune cells to fight breast cancer.

“And, rather than seeing the MMP-8 protein as a ‘bad cop’ in breast cancer, recent research has shown that levels of this protein are raised in women who do relatively well.

“Yet, until now, we haven’t known why this should be the case.

“But these are early findings from cells grown in a lab, and more research is needed to see if the molecules found by the scientists alert immune cells to cancers in women.”

Source: BBC