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Researchers Discover Gene That Plays Major Role In Parkinson's Disease

About 1 million Americans suffer from Parkinson's disease, and according to the Parkinson's Disease Foundation, a further 60,000 Americans are newly diagnosed with this complex neurodegenerative disorder every year.

The disease leads to disruptions in motor functions, such as tremors and slowed movements that are caused by a buildup of proteins within the nerve cells, which prevent the cells from communicating with each other. It can also lead to dementia. According to previous research, the substantia nigra, an area of the midbrain involved in controlling movement, loses neurons as Parkinson's disease progresses.

A recent study (BUSM) published online in PLoS Genetics revealed that the FOXO1 gene may play an important part in the pathological mechanisms of Parkinson's disease. The study involved the largest number of brain samples used in a whole-genome expression study of Parkinson's disease to date.

Research leader Alexandra Dumitriu, PhD, a postdoctoral associate in the department of neurology at Boston University School of Medicine (BUSM) and her team analyzed variations of gene expression in brain tissues of 27 samples with diagnosed Parkinson's disease and 26 samples from neurologically healthy controls. The team focused on eliminating potential sources of variation by minimizing the differences between samples by only using male brain tissue samples obtained from the prefrontal cortex, which showed no important signs of Alzheimer's pathology, and is one of the co-occurring common neurological diseases in patients suffering from Parkinson's disease.

All samples were of similar tissue quality and taken from the brain's prefrontal cortex, which, unlike the substantia nigra, has a lesser extent of neuronal death, and even though molecular and pathological modifications occur in this area during the process of the disease, it is also responsible for the development of dementia in a large percentage of Parkinson's disease patients.

The prefrontal cortex is not an area which is often studied.

The findings revealed that the FOXO1 gene, a transcriptional regulator that can alter the expression of other genes, showed increased expression in the brain tissue samples from diagnosed Parkinson's patients. Furthermore, the researchers discovered that two single-nucleotide polymorphisms (SNPs), i.e. variations in DNA sequence of the FOXO1 gene were substantially linked to the age at which Parkinson's disease had started.

Dumitriu concludes:

"Our hypothesis is that FOXO1 acts in a protective manner by activating genes and pathways that fight the neurodegeneration processes. If this is correct, there could be potential to explore FOXO1 as a therapeutic drug target for Parkinson's disease."

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