In a paper published in the journal Cell Death and Differentiation, a research team has reported 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. By discovering the gene networks that orchestrate the process of ATF4 expression, the 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.

The findings build upon recent research that discovered several genes that protect neurons in Parkinson’s disease, creating possibilities for new treatment options.

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.

Dysfunctional mitochondrial metabolism has been linked to Parkinson’s and research has previously showed that boosting this metabolism with nucleotides can protect neurons.

Paper: “dATF4 regulation of mitochondrial folate-mediated one-carbon metabolism is neuroprotective”
Reprinted from materials provided by University of Leicester.