University of Alabama researchers have identified five genes within animal models displaying protective capabilities against a hallmark trait of Parkinson's disease.
The research, publishing Jan. 8 in the Proceedings of the National Academy of Sciences' Early Edition, is a possible step toward identifying both new targets for drug treatment development and genetic factors which make some people more susceptible to the disease, the researchers said.
“We've found five genes so far that significantly protect dopamine neurons from dying within our animal models,” said Dr. Guy Caldwell, associate professor of biological sciences at UA and co-author of the research.
The UA researchers' efforts, Caldwell said, represents one of the largest functional analyses of genes ever reported for Parkinson's disease. Shusei Hamamichi, a UA doctoral student, is lead author of the research paper and led the University's effort, along with Renee Rivas and Adam Knight, two UA undergraduates, Songsong Cao, a former doctoral student, Dr. Kim Caldwell, assistant professor of biological sciences, and Guy Caldwell.
Hamamichi's role represents a “heroic effort,” Guy Caldwell said.
UA researchers used specific strains of tiny nematode worms as animal models for the research. These genetically engineered worms contain a human protein, alpha-synuclein, within their cells. Scientists have learned that people with too many copies of the code for alpha-synuclein within their DNA will contract Parkinson's.
Extra copies of alpha-synuclein can lead to repeated protein misfolding and death of the dopamine producing neurons in the brain. In Parkinson's patients, the death of these neurons leads to rigid and tremoring limbs, difficulty in movement and impaired reflexes. More than 1 million Americans are estimated to have Parkinson's.
Utilizing bioinformatic databases – which contain an abundance of information related to various genes and their genetic associations – the UA researchers first mined the data, prioritizing 867 genes for testing.
Using a revolutionary technique known as RNA interference, or RNAi, Hamamichi removed, one at a time, the functions of each of the 867 genes from the tiny nematodes. This, Caldwell said, enabled the research team to investigate the impact the missing function would have on cellular processes.
“Of these approximate 900 genes, we narrowed it down to 20 top candidates that seemed to have the most significant affect on alpha-synuclein aggregation as the animals aged,” Caldwell said.