- 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.''
1-Oct-2007 (News-Medical.net)