Genes That Shield Dopamine Neurons From Death Identified

Scientists report new research invaluable in the management of Parkinson’ disease.

This discovery can act as an important step towards identifying both new targets for drug treatment development and genetic factors that make some people more vulnerable to the disease.

The study is led by Shusei Hamamichi, a UA doctoral student with the help of his tam including Dr. Guy Caldwell, associate professor of biological sciences at UA, who said that this research is one of the largest functional analyses of genes ever reported for Parkinson's disease.

“We’ve found five genes so far that significantly protect dopamine neurons from dying within our animal models,” said Dr. Caldwell.

For the study, the researchers used specific strains of tiny nematode worms as animal models. These genetically engineered worms contain a human protein, alpha-synuclein, within their cells. The researchers observed 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. The death of these neurons leads to rigid and tremoring limbs, difficulty in movement and impaired reflexes, in Parkinson’s patients.

First, the UA researchers made use of bioinformatic databases, which contain an abundance of information related to various genes and their genetic associations, in order to mine the data, prioritizing 867 genes for testing.

The researchers used a revolutionary technique known as RNA interference, or RNAi, and removed, one at a time, the functions of each of the 867 genes from the tiny nematodes.

According to Caldwell, this enabled the researchers 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,” said Caldwell.

Caldwell also added that, importantly, secondary screening of the 20 genes has revealed five offering dopamine neurons protection from dying.

The study was published recently in the Proceedings of the National Academy of Sciences’ Early Edition.

Source-ANI
LIN/K