As the flies aged, they developed Parkinson’s-like symptoms – including impaired movement and loss of brain cells – mirroring key aspects of disease progression seen in humans.
Using large-scale genetic screening made possible by the fruit fly model, the researchers systematically identified genes involved in α-synuclein-induced toxicity. Among these, the gene mino stood out for its strong effects on disease-related symptoms, leading the team to investigate its role further. This gene codes for the enzyme glycerol-3-phosphate acyltransferase (GPAT) and plays a key role in regulating fat metabolism in cells.
When the scientists reduced the activity of the mino gene, the flies experienced less loss of brain cells, improved movement, and healthier activity patterns. In contrast, increasing the gene’s activity worsened the flies’ symptoms.
The researchers then explored whether blocking GPAT could help counter these toxic effects. They tested a compound called FSG67, which blocks the activity of GPAT and has previously been studied in laboratory settings for obesity-related and metabolic disorders.
When the flies were treated with FSG67, the harmful effects of α-synuclein – including protein clumping and fat damage – were reduced. The scientists observed similar protective effects in mouse brain cells grown in the laboratory.
Going forward, the scientists will focus on further validating these findings and exploring the possibility of developing GPAT inhibitors as a new class of drugs for Parkinson’s disease. ScienceMission sciencenewshighlights.
