Researchers are studying the causes of premature ageing of neurons in Parkinson’s patients with a defective DJ1 (PARK7) gene. The genetic defect causes changes in the cellular metabolism meaning that neurons are subjected to oxidative stress and an increased immune response in the brain. The study has just been published in the scientific journal Neurobiology of Disease.
Parkinson’s disease, the second most common neurodegenerative disease, has genetic causes in 15% of cases. Premature ageing of dopaminergic neurons in the substantia nigra in the brain is the reason for the motor symptoms that characterise this disease. However, how this happens is not yet fully understood.
In the current study, researchers looking for the answer in metabolism investigated a specific form of Parkinson’s disease with a defective DJ1 gene and discovered that two key metabolic pathways are affected.
The research team was also able to show that mutations in the DJ1 gene can also negatively affect other cells in the brain. Microglial cells, which are responsible for the immune reaction in the brain, become 'hyperactive' when the DJ1 gene is defective.
Interestingly, the researchers were able to determine metabolic changes not only in the brain’s immune cells but also in the blood of Parkinson’s patients with mutant DJ1. This could lead to new diagnostic avenues in the future.
The next step will involve investigating how affected metabolic pathways can be influenced using drugs. The changes described in glutamine and serine metabolic processes could thus be used to develop novel approaches for treating Parkinson’s.
Source: University of Luxembourg