Out-of-whack protein may boost Parkinson's

February 26, 2008

A single change in a protein may play a role in whether someone develops Parkinson’s disease, say University of Florida Genetics Institute researchers writing in a recent issue of the Proceedings of the National Academy of Sciences.

Scientists studying rats induced to display a form of Parkinson’s disease discovered that a protein commonly found in brain cells can be toxic if — at one pinpoint location in its amino acid structure — it lacks a chemical compound called a phosphate.

When scientists used gene therapy to simulate a phosphate at this critical position, the rats’ brain cells didn’t develop the Parkinson-like pathology that would normally occur.

The finding provides new insight into the fundamentals of Parkinson’s disease and the role of an abundant yet mysterious brain protein known as alpha-synuclein, which is believed to help brain cells communicate but may have a more sinister role in the development of neurological diseases.

“We have another potential target for therapy, but there is a great deal left to discover,” said Nicholas Muzyczka, Ph.D., a professor of molecular genetics and microbiology in the College of Medicine and an eminent scholar with the UF Genetics Institute. “This is one more piece of information about what might be causing the toxicity in Parkinson’s disease, and it gives us a little more to go on about what alpha-synuclein does in the brain.”

Generally located at the synapses of nerve cells, alpha-synuclein is believed to aid in brain function, possibly by helping cells communicate with one another by controlling the release of neurotransmitters such as dopamine.

Mutations of alpha-synuclein may cause a rare, inherited form of Parkinson’s, and the protein has been found to be the major component of Lewy bodies, which are abnormal clusters of protein in the brain cells of patients with Parkinson’s disease.

The National Parkinson Foundation estimates 1.5 million Americans currently have Parkinson’s disease and about 60,000 new cases are diagnosed each year. It is caused by the death or impairment of certain nerve cells in a part of the brain called the substantia nigra. When these cells die, the body is deprived of dopamine, a neurotransmitter vital for movement.

“We know of several enzymes that can cause phosphorylation in the proper position of the alpha-synuclein protein,” said Oleg Gorbatyuk, Ph.D., an assistant professor of molecular genetics and microbiology. “Increasing their expression in brains afflicted with Parkinson’s disease could possibly provide a gene therapy approach to the disease.”

In experiments described in the Jan. 15 issue of PNAS, UF researchers used gene transfer to enhance the production of three versions of alpha-synuclein in the substantia nigra region on one side of the rats’ brains. The other side was not treated, for comparison purposes.

Of the types of alpha-synuclein, the one that simulated phosphorylation at position 129 of the protein was nontoxic. But the other versions of the protein all caused significant loss of dopamine neurons in the substantia nigra.

“Adding a phosphate group is about the smallest thing that can possibly happen in biology,” said Mark R. Cookson, an investigator in the Cell Biology and Gene Expression Unit of the National Institute on Aging who was not involved in the research. “But this relatively minor, innocuous change can switch everything around from being a big problem to being no problem. This research really gives us an idea of some things going on in inherited cases of Parkinson’s disease, and if we use that genetic information as a handle to get into the common disease, it is possible to take this from genetics to a drug discovery program.”

Source: University of Florida

Explore further: Scientists demonstrate path to linking the genome to healthy tissues and disease

Related Stories

Scientists demonstrate path to linking the genome to healthy tissues and disease

October 13, 2017
Our genomes help to determine who we are - the countless variations between individuals that encode the complexity of tissues and functions throughout the body. Since scientists first decoded a draft of the human genome more ...

Scientists solve 3-D structure of key defense protein against Parkinson's disease

October 5, 2017
Scientists at the University of Dundee have identified the structure of a key enzyme that protects the brain against Parkinson's disease.

Novel protein interactions explain memory deficits in Parkinson's disease

September 26, 2017
A study published in the journal Nature Neuroscience describes the identification of a novel molecular pathway that can constitute a therapeutic target for cognitive defects in Parkinson's disease. The study showed that abnormal ...

Parkinson's disease drug shows anticancer effects

September 28, 2017
Research shows the Parkinson's disease drug carbidopa displays significant anticancer effects in both human cell lines and mice when given at normal patient dosage levels.

Researchers find new path to promising Parkinson's treatment

September 19, 2017
Three researchers at The University of Alabama are part of work that is leading to a new direction for drug discovery in the quest to treat Parkinson's disease.

Tug of war between Parkinson's protein and growth factor

September 18, 2017
Alpha-synuclein, a sticky and sometimes toxic protein involved in Parkinson's disease (PD), blocks signals from an important brain growth factor, Emory researchers have discovered.

Recommended for you

New approach helps rodents with spinal cord injury breathe on their own

October 17, 2017
One of the most severe consequences of spinal cord injury in the neck is losing the ability to control the diaphragm and breathe on one's own. Now, investigators show for the first time in laboratory models that two different ...

Pair of discoveries illuminate new paths to flu and anthrax treatments

October 17, 2017
Two recent studies led by biologists at the University of California San Diego have set the research groundwork for new avenues to treat influenza and anthrax poisoning.

New method to measure how drugs interact

October 17, 2017
Cancer, HIV and tuberculosis are among the many serious diseases that are frequently treated with combinations of three or more drugs, over months or even years. Developing the most effective therapies for such diseases requires ...

A new compound targets energy generation, thereby killing metastatic cells

October 17, 2017
Cancer can most often be successfully treated when confined to one organ. But a greater challenge lies in treating cancer that has metastasized, or spread, from the primary tumor throughout the patient's body. Although immunotherapy ...

Research finds that zinc binding is vital for regulating pH levels in the brain

October 17, 2017
Researchers in Oslo, Norway, have discovered that zinc binding plays an important role in the sensing and regulation of pH in the human brain. The findings come as one of the first studies that directly link zinc binding ...

Researchers find factor that delays wound healing

October 17, 2017
New research carried out at The University of Manchester has identified a bacterium—normally present on the skin that causes poor wound healing in certain conditions.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.