New discovery drug in Parkinson’s disease

New discovery drug in Parkinson’s disease

Researchers funded by the National Institutes of Health have turned simple baker's yeast into a virtual army of medicinal chemists capable of rapidly searching for drugs to treat Parkinson's disease. In a study published online today Nature Chemical Biology, the researchers showed that they can rescue yeast cells from toxic levels of a protein implicated in Parkinson's disease by stimulating the cells to make very small proteins called cyclic peptides. Two of the cyclic peptides had a protective effect on the yeast cells and on neurons in an animal model of Parkinson's disease.
Parkinson's disease attacks cells in a part of the brain responsible for motor control and coordination. As those neurons degenerate, the disease leads to progressive deterioration of motor function including involuntary shaking, slowed movement, stiffened muscles, and impaired balance. The neurons normally produce a chemical called dopamine. A synthetic precursor of dopamine called L-DOPA or drugs that mimic dopamine's action can provide symptomatic relief from Parkinson's disease. Unfortunately, these drugs lose much of their effectiveness in later stages of the disease, and there is currently no means to slow the disease's progressive course. Investigators have discovered that vulnerable brain cells in patients with Parkinson's disease accumulate a protein called alpha-synuclein. Moreover, genetic abnormalities in alpha-synuclein cause a rare familial form of the disease. When yeast cells are engineered to produce large amounts of human alpha-synuclein, patient will die.
Cyclic peptides are fragments of protein that connect end-to-end to form a circle. Although cyclic peptides are synthetic, they resemble structures that are found in natural proteins and protein-based drugs, including pain killers, antibiotics and immunosuppressants. Cyclic peptides that suppress alpha-synuclein toxicity could be candidate drugs for Parkinson's disease, or they could help researchers identify new drug targets for the disease.
A procedure involves exposing yeast cells to short snippets of DNA that the cells can absorb and use to make cyclic peptides. Then, he flips the genetic switch that causes the cells to produce toxic levels of alpha-synuclein. If the yeast make cyclic peptides that suppress alpha-synuclein toxicity, they live; if not, they die. This simple assay enables testing millions of cyclic peptides simultaneously in millions of yeast cells. The process is extremely rapid and much less expensive compared to other techniques used to screen large number of chemicals with an eye toward new drugs.