Parkinson's disease researchParkinson’s disease (PD) is the second most common progressive neurodegenerative disorder, after Alzheimer's disease.
It is characterized by four main symptoms, caused by the lack of the neurotransmitter dopamine: shaking or rhythmic
movement, stiffness of the limbs, slowness of movement, and poor balance and coordination. It usually occurs later
in life, with an average age of onset of 62.4 years for patients in the United States. In Parkinson’s disease, for
reasons that are not fully explained yet, dopaminergic neurons in the region of the brain called
substantia nigra
begin to malfunction and eventually die. This causes a decrease in the amount of the available dopamine, which
transports signals to the parts of the brain that control movement initiation and coordination.
Even though the mechanism that triggers the dopaminergic neurons’ death in Parkinson’s is not entirely understood,
most scientists believe that genetic factors play an important role. Indeed, it is estimated that about 15-25% of
Parkinson’s patients report having a relative that also has the disease.
In this work, we use our combinatorial optimization models to identify different gene expression profiles in a dataset
introduced by
Brown et al. (2002). The dataset
has the expression of 7,139 genes (and ESTs) in 80 samples. The samples were taken from 40 different regions of the brains
of a Parkinson-affected rodent and of a control which is labeled "normal".
We created four genetic signatures with different numbers of genes, and their union contains 77 genes. From those,
for 33 we could support a potential link with neurodegenerative diseases or known processes. Among the main pathways with representatives are Parkinson's,
Alzheimer's and Huntington's diseases, as well as apoptosis signalling, p53 signalling and cadherin signalling.
For more information about this line of research, please refer to the publication:
Genetic Signatures for a Rodent Model of Parkinson's Disease Using Combinatorial Optimization Methods
M. Hourani, R. Berretta, A. Mendes and P. Moscato, in:
Bioinformatics,
Humana Press (in print).
