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Single Gene Mutation Increases Risk of Earlier Onset Parkinson's Disease

by Sheela Philomena on November 3, 2016 at 11:30 AM
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Highlights

Single mutation in the PTEN-induced putative kinase 1 (PINK1) gene confers a risk for the development of Parkinson's disease.


A study conducted in 7 countries with a collaboration of 32 researchers finds that people with earlier onset Parkinson's disease inherited mutations in both PINK1 alleles (one from each parent).

‘Single mutated PTEN-induced putative kinase 1 (PINK1) gene may confer an increased risk of developing Parkinson�s disease. ’

"We know that if you have mutations in both copies of PINK1, age at onset of Parkinson's will usually be younger than 45. This study showed that if a person inherited a specific mutation in just one PINK1 gene, the disease could develop at about age 55 or so. By contrast, the most common, nonfamilial forms of Parkinson's develop at about age 65," says the study's senior investigator, Wolfdieter Springer, Ph.D., a neuroscientist at Mayo Clinic's Florida campus.

Genetic studies had suggested that a single mutated PINK1 allele might confer an outsized risk of the developing the disease. It took a "very effective synergetic" effort of clinical, structural and cell biologists, along with geneticists and data from thousands of affected patients, to show how it led to earlier disease development, Dr. Springer says. "It took a real international collaboration to solve this puzzle," he says.

Role of PINK1 Gene

PINK1 works along with PARKIN gene to ensure that mitochondria (cell's power plant) in neurons remain healthy. Neurodegenerative disorders are characterized by disruption in energy production in neurons.

Quality Control System of Mitochondria

During the functioning process, proteins produced from both PINK1 and PARKIN genes work together to ensure safe disposal of damaged mitochondria from the cell.

Protein marker produced during the process is labeled to the damaged mitochondria that need to be destroyed.

Mutations in PINK1 and PARKIN gene result in energy production in neurons leading to its death which predisposes the risk for neurodegenerative disorders.

Dr. Springer says, "Specific mutation (p.G411S) in one copy of PINK1 substantially impairs this same pathway by inhibiting the protein produced from other healthy PINK1 allele. This rare mutation has an outsized effect, and the remaining levels of functional PINK1 protein are not enough to cope with damaged mitochondria,"

The study had started with genetic findings when one of the lead authors, Andreas Puschmann, M.D., Ph.D., of the Department of Neurology, Sk책ne University Hospital, Sweden, was a visiting scientist at Mayo Clinic. Additional structural and cell biological data then provided the sought-after mechanism to explain the observed phenomenon.

The findings could have implications for other neurodegenerative disorders. Study published in Brain

Source: Medindia

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