NTU Singapore Scientists Identify Fat-Producing Enzyme GPAT as "Double Hit" Driver of Parkinson’s Damage

NTU Singapore researchers identify GPAT enzyme as a driver of Parkinson's brain damage, showing that blocking it reduces cell death and improves movement.

By: AXL Media

Published: Apr 9, 2026, 11:11 AM EDT

Source: Information for this report was sourced from Nanyang Technological University, Singapore.

The "Double Hit" to Brain Energy and Stability

In a study published in Nature Communications, scientists from NTU’s Lee Kong Chian School of Medicine (LKCMedicine) revealed a lethal synergy between fat metabolism and the protein $\alpha$-synuclein, which is known to clump in the brains of Parkinson’s patients. The research team found that the enzyme GPAT triggers a "double hit" mechanism: it impairs mitochondria (the cell's "power stations"), reducing the energy available for brain cells to function, while simultaneously increasing the inherent toxicity of $\alpha$-synuclein. This dual disruption accelerates the loss of neurons, leading to the hallmark tremors and motor impairments of the disease.

Genetic Screening via Fruit Fly Models

The breakthrough was achieved through large-scale genetic screening of fruit flies engineered to produce excess human $\alpha$-synuclein. As these flies aged, they exhibited symptoms mirroring human Parkinson's progression. Researchers identified the gene mino—which codes for GPAT—as a primary culprit in disease severity. When activity of the mino gene was reduced, the flies showed significantly less brain cell loss and improved movement patterns. Conversely, overactivating the gene worsened the Parkinson's-like symptoms, confirming GPAT's role as a key driver of neurodegeneration.

Blocking the Enzyme: A New Therapeutic Strategy

To test the potential for treatment, the NTU team utilized a chemical compound called FSG67, a known GPAT inhibitor previously explored for metabolic disorders like obesity. Treatment with FSG67 led to: