Parkinsons

Parkinson's Disease

Parkinson's disease is a degenerative disorder of the central nervous system. The motor symptoms of Parkinson's disease result from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain; the cause of this cell death is unknown.

Several early sources, including an Egyptian papyrus, an Ayurvedic medical treatise, the Bible, and Galen's writings, describe symptoms resembling those of PD. After Galen there are no references unambiguously related to it until the 17th century. Early neurologists who made further contributions to the knowledge of the disease include Trousseau, Gowers, Kinnier Wilson. Erb, and most notably Jean-Martin Charcot, whose studies between 1868 and 1881 were a landmark in the understanding of the disease. Among other advances, he made the distinction between rigidity, weakness and bradykinesia. He also championed the renaming of the disease in honor of James Parkinson. In 1912 Frederic Lewy described microscopic particles in affected brains, later named "Lewy bodies". In 1919 Konsiantin Tretiakoff reported that the substantia nigra was the main cerebral structure affected, but this finding was not widely accepted until it was confirmed by further Studies published by Roll Hassler in 1938. The underlying biochemical changes in the brain were identified in the 1950s, due largely to the work of Arvid Carlsson on the neurotransmitter dopamine and its role on PD- In 1997, alpha-synuclein was found to be the main component of Lewy bodies.

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 especiallv 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 ceils in the hope that differences between the two would explain why the sensitive cells die. This understanding would 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 Rockefeller University have developed a system that solves this fundamental technological problem. These scientists have focused on discovering which genes are turned on and 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 on. When genes are "turned on", they cause the cell to product specific proteins.

What makes cells vulnerable to Parkinson's disease depends largely on the kinds and amounts of proteins they punitive, or their "translational profile." The new method discovered by Greengard. Hainan, 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 among the hundreds of specialized cell types that are tangled together in the brain tissues, toward a belter 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.