Gene that lowers cell stress could protect against Parkinson’s disease

Oct 1 2007

The discovery of a relationship between two cell enzymes and their role in keeping the cell's energy generating machinery working smoothly could provide a new target for development of therapies for Parkinson's disease (PD).

Research led by Dr L.Miguel Martins of the MRC Toxicology Unit at the University of Leicester and Dr Julian Downward of the Cancer Research UK London Research Institute has shown that the products of two genes called HtrA2 and PINK1 co-operate in preventing breakdown of cell function that could otherwise lead to Parkinson’s symptoms. The research is published online in Nature Cell Biology.

Dr Martins explained: ‘‘It is already known that mutations in genes linked to the mitochondria, the powerhouse of the cell, can make a person susceptible to PD. What was not clear, until recently, was the contribution made by the HtrA2 enzyme in keeping the mitochondria running smoothly.’’

The team has discovered that HtrA2 interacts with a second enzyme called PINK1 in times of cell stress to prevent the mitochondria from breaking down. And that this preservation of the mitochondria’s function has a protective effect by interrupting a pathway that might otherwise lead the cell to stop working which in turn generates wider symptoms like those of PD.

‘‘We already knew that defects in HtrA2 and PINK1 are linked to Parkinson’s disease symptoms because mutations in these two genes are found in Parkinson’s disease patients. The aim of our research was to determine if these two genes cooperate ’’ Dr Martins added.

The research suggests that if a person has an abnormal copy of the PINK1 gene, this contributes to development of Parkinson’s disease by affecting the HtrA2 protein.

Dr Martins concluded: ‘‘By protecting the mitochondria, PINK1 and HtrA helps to limit environmental stress within the cell and maintain healthy function. Without these, the cell can’t function properly. This could explain cases of PD that seem to arise sporadically. Overall, the description of the HtrA2 pathway in response to cell stress will lead to improved understanding of the development of Parkinson’s disease and in the long-term hopefully to new therapeutic targets.’’