Guido Bommer receives the viscountess de Spoelberch prize


Parkinson’s disease is a common neurodegenerative disease, but we still do not understand why it develops. We have discovered that some familial forms of Parkinson’s disease are caused by damage of molecules that occurs when cells break down sugar. We are currently trying to understand how this type of damage might contribute to the development of Parkinson’s disease.

It remains unclear why Parkinson’s disease develops

Parkinson’s disease is a slowly progressive, severe neurodegenerative disease. We know that specific cells in the brain die, and that specific proteins aggregate, but we do not understand why these changes occur in some patients and not in many other persons. It has long been suspected that the accumulation of molecular damage during a lifetime might contribute to the development of Parkinson’s disease. However, it is unclear what these changes might be.

The gene PARK7 is inactivated in rare early-onset cases of Parkinson’s disease, but its function remains enigmatic

Most cases of Parkinson’s disease occur in patients over 55 years of age, but sometimes the disease occurs much earlier. Some of these ‘early-onset’ cases are due to mutations in specific genes. One of this genes is called PARK7. Despite more than 2000 publications on PARK7, the function of the enzyme encoded by the PARK7 gene still remained elusive.

PARK7 protects cells from damage caused by the metabolism of sugar

We have discovered that PARK7 prevents damage caused by a reactive compound that forms in all cells that metabolize a specific sugar called glucose. Many cells in our body and in particular the brain rely on glucose as their energy supply. Glucose is broken down in cells in a series of chemical reactions leading to smaller and smaller fragments. One of the things that we have discovered is that one of these fragments (1,3-bisphosphoglycerate) gets spontaneously converted to an extremely reactive compound (cyclic 1,3-phosphoglycerate) that had never been described and that can damage proteins (i.e. the workhorses of a cell) and metabolites (i.e. small molecules that form when our body breaks down or produces more complex structures). Our other discovery is that PARK7 destroys the reactive compound and thereby prevents the damage. PARK7 function is extremely conserved, given that the inactivation of PARK7 in flies, mice and human cell lines leads to the accumulation of similarly damaged metabolites or proteins. Furthermore, the function of PARK7 in human cells can be replaced when we reintroduce related proteins from yeast or bacteria.

Why is this relevant?

We have identified the origin of one type of damage that is formed almost universally in all cells, and which can be prevented by the enzyme PARK7. This finding might lead to the development of pharmacological or dietary interventions that help patients with PARK7 defects. PARK7 is easily inactivated by oxidative stress that can develop for many reasons. This suggests that loss of PARK7 function and accumulation of a similar type of damage might be responsible for the formation of Parkinson’s disease in a wider range of patients. As a consequence, it is conceivable that the above-mentioned pharmacological or dietary interventions might also work for these patients. We discovered that a metabolite from glycolysis (i.e. the central way how cells break down sugar) causes damage that likely causes Parkinson’s disease. It is quite rare that fundamental aspects of key metabolic pathways are being discovered. It is even rarer that these findings have direct implications for a complex human disease.

Guido Bommer and his team From left to right: Stéphanie Paquay, Jean Jacob, Guido Bommer, Isabelle Gerin, Isaac Heremans, Francesco Caligiore, Emilie de Kerchove

Article describing this research

Parkinson's disease protein PARK7 prevents metabolite and protein damage caused by a glycolytic metabolite.
Heremans IP, Caligiore F, Gerin I, Bury M, Lutz M, Graff J, Stroobant V, Vertommen D, Teleman AA, Van Schaftingen E & Bommer GT
PNAS (2022) 119(4): e2111338119