Novel tool helps study the biochemical basis of Alzheimer's

A new study being published in this Friday's online edition of Cell will help answer the question, what causes Parkinson's disease?

One of the most pressing questions in the medical research into Parkinson's disease is what causes the sensitive cells in the brain to die in the first place. Answering this question has been especially difficult because there are two nearly identical types of brain cells that produce dopamine and they are mixed together in the same brain regions. However, only one cell type is affected in Parkinson's, the other is spared. Scientists have wanted to compare these closely related brain cells in the hope that differences between the two would explain why the sensitive cells die. This understanding will suggest opportunities for intervention.

The main obstacle has been the infeasibility of separating the two cell types for analysis. Doctors Paul Greengard and Myriam Heiman of The Michael Stern Parkinson's Disease Foundation and their colleagues at The Rockefeller University have developed a system that solves this fundamental technological problem. These scientists have focused on discovering which genes are turned on or off in the two similar cell types. If one views a cell as a computer, then the genes can be viewed as software. Unique programs operate depending on which genes are turned on. When genes are "turned on", they cause the cell to produce specific proteins.

What makes cells vulnerable to Parkinson's disease depends largely on the kinds and amounts of proteins they produce, or their "translational profile."

The new method discovered by Greengard, Heiman, and colleagues, Translating Ribosome Affinity Purification (TRAP), reveals translational profiles in cells by isolating the genetic messages as they pass through the protein production factories called ribosomes.

This new technique will help propel the scientific community, which has struggled to sleuth out the subtle molecular differences amongst the hundreds of specialized cell types that are tangled together in the brain tissues, toward a better understanding of the causes of Parkinson's disease.

"We can look at a thousand genes instead of one at a time, so things should clear a thousand times faster," says Greengard.

The novel TRAP tool will also help study the biochemical basis of Alzheimer's, Huntington's and other neurological diseases.

Finding the cause, developing treatments and discovering the cure for Parkinson's disease is the focus of The Michael Stern Parkinson's Research Foundation. Established in 2001 to support and expand the pioneering research of Paul Greengard, Nobel laureate, at The Rockefeller University and select academic research centers in the U.S.

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