Protein kinase target emerges in Parkinson's
mutations that cause symptoms associated with Parkinson's disease
and other neurodegenerative disorders.
The team found a mutation of the gene, named LRRK2, in members of six families with many individuals affected by Parkinson's disease. Surprisingly, brain autopsy on deceased, affected family members who participated in this research indicate mutations in the LRRK2 gene play a central role in developing pathology characteristic of Parkinson's disease and other neurodegenerative disorders such as Alzheimer's disease and amyotrophic lateral sclerosis (also known as motor neuron disease).
Their discovery is reported in the 18 November issue of the journal Neuron.
Mayo Clinic neurologist Dr Zbigniew Wszolek, who studied the two largest families in which a LRRK2 mutation was found, said: "the discovery of this gene will have major implications for the understanding of mechanisms leading to the development of these neurodegenerative diseases."
"We also hope that continued study of this gene will lead to curative treatments for Parkinson's disease and other similar conditions."
The gene appears to code for a protein kinase, which could provide a fast route to new pharmacological therapies for the disease. Kinases are a fast-growing sector in drug discovery and have already yielded effective new drugs for cancer and other diseases.
The discovery is the culmination of research into the cause of autosomal dominant, late-onset Parkinson's disease in the studied families. This team and others have previously narrowed a genetic cause for this form of inherited parkinsonism to a region of chromosome 12 called PARK8.
The team conducted genetic analyses on DNA collected from family members to reveal the culprit gene and the multifunctional protein for which it codes, while subsequent brain tissue studies revealed for the first time one gene was responsible for a range of pathology associated with a host of neurodegenerative disorders.
These studies revealed sufferers uniformly exhibited pathology consistent with Parkinson's disease, while some exhibited additional pathology associated with either diffuse Lewy body disease, Alzheimer's disease or ALS.
Parkinson's disease is the second most common neurodegenerative disease, affecting up to 50 per cent of individuals over age 85.
