Parkinson’s Disease
Introduction
Parkinson's disease was first described in 1817 by the English physician James
Parkinson as the "shaking palsy". This common chronic progressive disorder of late
adult life manifests as tremors of the hands, muscular rigidity, slowness of
movement and a stooped posture and shuffling gait.
About 50,000 Americans are diagnosed with the disease each year. This is a
mysterious disease with no known cause or cure. The cause of Parkinson's disease
is currently thought to be a combination of environmental and genetic factors.
Research
Scientists at the National Human Genome Research Institute (NHGRI) have
identified a gene that encodes a protein called alpha synuclein. Studies of an
abnormal version of the gene revealed a mutation in a single base pair. Because the
normal gene plays a role in the function of nerve cells, the finding gives
researchers a powerful new tool for understanding cellular abnormalities in
Parkinson's disease.
The paper confirms an earlier report by the same research group of an Italian
family with a genetic predisposition to one form of Parkinson's disease. That
study showed that the gene responsible was situated somewhere in a large region
on the long arm of chromosome 4. Until that report, the consensus was that
environmental toxins were the primary cause Parkinson's disease.
Using data obtained through the Human Genome Project, the researchers rapidly
located the mutation to a region of the genome containing approximately 100
genes. One of the genes already placed in this interval was alpha synuclein. The
alpha synuclein gene was an excellent candidate for being a Parkinson's disease
gene because previous research had already shown that the amyloid plaques of
Alzheimer's disease patients contained fragments of the alpha synuclein protein.
Considering its potential role in neurodegenerative disease, the researchers began
looking at the precise sequence of alpha synuclein in normal and affected
individuals. In the Italian family and three of the Greek families, the Parkinson's
patients were found to possess an identical mutation in a single base pair of the
alpha synuclein gene.
Deposits in the brain called Lewy bodies distinguish Parkinson’s disease. The
researchers hypothesize the mutation in the synuclein protein causes it to
aggregate, thus attracting other proteins to form a deposit that damages the cell.
A similar mechanism has been proposed for the production of amyloid plaques in
Alzheimer's disease. The finding that Alzheimer's disease plaques contain a
fragment of alpha synuclein further strengthens the idea that a common
mechanism may be operating in both of these neurodegenerative diseases.
The NHGRI researchers believe that the abnormal gene is responsible for a
significant portion of familial Parkinson's disease with onset generally before the
age of 60. It remains to be seen whether these alterations will also be involved in
other forms of the disease with later onset and less familial history. The
researchers are now looking at related synuclein genes among patients with a
familial history of Parkinson's disease but no defect in the alpha synuclein gene.
Homework done by:
Camilo Mancera Arias