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Genetic ‘switch’ may prevent Parkinson’s disease

Sunday, Feb 19, 2017,14:51 IST By anju A A A

London | Scientists have identified a key genetic ‘switch’ that may help prevent or delay the symptoms of Parkinson’s disease.

Researchers at the University of Leicester in the UK found that a gene called ATF4 plays a key role in Parkinson’s disease, acting as a ‘switch’ for genes that control mitochondrial metabolism for neuron health.

“When the expression of ATF4 is reduced in flies, expression of these mitochondrial genes drops,” said Miguel Martins from the University of Leicester.

This drop results in dramatic locomotor defects, decreased lifespan, and dysfunctional mitochondria in the brain,” said Martins.

“Interestingly, when we over-expressed these mitochondrial genes in fly models of Parkinson’s, mitochondrial function was reestablished, and neuron loss was avoided,” Martins added.

By discovering the gene networks that orchestrate this process, researchers have singled out new therapeutic targets that could prevent neuron loss.

Some forms of Parkinson’s are caused by mutations in the genes PINK1 and PARKIN, which are instrumental in mitochondrial quality control.

Fruit flies with mutations in these genes accumulate defective mitochondria and exhibit Parkinson’s-like changes, including loss of neurons.

The researchers used PINK1 and PARKIN mutant flies to search for other critical Parkinson’s genes – and using a bioinformatics approach discovered that the ATF4 gene plays a key role.

“Studying the roles of these genes in human neurons could lead to tailored interventions that could one day prevent or delay the neuronal loss seen in Parkinson’s,” said Martins.

Two of the genes – PINK1 and PARKIN – affect how mitochondria break down amino acids to generate nucleotides – the metabolism of these molecules generates the energy that cells need to live.

The study was published in the journal Cell Death and Differentiation.