Parkinson's patients display a variety of motor and non-motor symptoms, impeding their ability to perform basic everyday activities. With currently no effective therapy, the chronic and progressive nature of Parkinson's disease has a profound impact on the quality of life of patients and caregivers.
Screening DNA of Parkinson's patients in the Christine Van Broeckhoven laboratory, the team from VIB (the Flanders Institute for biotechnology) identified a new risk gene called ATP10B for Parkinson's disease.
Mutations in ATP10B resulted in loss of ATP10B protein.
The function of the ATP10B gene was revealed by the Peter Vangheluwe lab (KU Leuven, Laboratory of Cellular Transport Systems) who identified ATP10B as a transporter for glucosylceramide, a lipid that plays a central role in Parkinson's disease.
Disease mutations disturb this function. Also, a reduced expression of ATP10B leads to neuronal loss and sensitizes neurons to environmental risk factors of Parkinson's disease.
Therefore, ATP10B is emerging as an interesting therapeutic target for Parkinson's disease.
"The identification of Parkinson's disease genes and mutations contributed substantially to our understanding of the underlying disease mechanisms. In 5 to 15 per cent of Parkinson's patients, genetic studies identified mutations in different genes that explained the segregation of disease in Parkinson's families between generations," the authors wrote.
Mutations in ATP10B were identified by researcher Stefanie Smolders in the VIB-UAntwerpen laboratory in children with Parkinson's disease at early age while the parents were healthy.
These children carried two mutations in ATP10B, one on each chromosome inherited from the parents, mimicking recessive inheritance.
In a group of 617 unrelated Parkinson's patients, she identified another six carriers of two ATP10B mutations.
"Among the carriers, we observed a high variability in the onset age at disease. This can indicate that the combination of multiple mutations might have different effects on ATP10B expression leading to variable losses of ATP10B protein and function," the authors explained.
According to Shaun Martin in the KU Leuven team, ATP10B is important to preserve the health of the lysosomes and protects neuronal cells against environmental risk factors of Parkinson's disease.
"A better understanding of key targets and pathways in Parkinson's disease pathogenesis is necessary to overcome the major hurdle in the development of effective therapies for the disease," the authors wrote.