Discovery of Genetic 'Switch' Could Prevent Symptoms of PD A genetic 'switch' has been discovered by MRC researchers at the University of Leicester which could help to prevent or delay the symptoms of Parkinson's disease (PD). The team discovered that a gene called ATF4 plays a key role in PD, acting as a 'switch' for genes that control mitochondrial metabolism for neuron health. If mitochondrial metabolism is affected, the neurons cease to function well. It has long been recognised that mitochondrial dysfunction is critically involved in the demise of dopaminergic neurons in PD and many of The Cure Parkinson's Trust's (CPT) research projects are targeting this important research area. Dr Miguel Martins from the MRC Toxicology Unit at the University of Leicester, who led the recent research, explained: "When the expression of ATF4 is reduced in flies, expression of these mitochondrial genes drops. This drop results in dramatic locomotor defects, decreased lifespan, and dysfunctional mitochondria in the brain. Interestingly, when we over-expressed these mitochondrial genes in fly models of Parkinson's, mitochondrial function was reestablished, and neuron loss was avoided." By discovering the gene networks that orchestrate this process, the researchers have singled out new therapeutic targets that could prevent neuron loss. Some forms of PD 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 PD-like changes, including loss of neurons. The researchers used PINK1 and PARKIN mutant flies to search for other critical PD genes, and using a bioinformatics approach discovered that the ATF4 gene plays a key role. Dr Martins added: "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." These findings build upon recent research by the University of Leicester team, which recently discovered several genes that protect neurons in PD, creating possibilities for new treatment options. The PINK1 and PARKIN genes affect how mitochondria break down amino acids to generate nucleotides -- the metabolism of these molecules generates the energy that cells need to live. CPT is also funding the research of a drug which targets the area between the PINK1 and PARKIN genes where the ATF4 gene expression is located. Read the full article here - Cell Death & Differentiation.