Looking into the cells of fruit flies could reveal the future of Parkinson treatment for humans
Genetic and Pharmacologic Modulation of Lysosomal Stress and Sphingolipid Homeostasis in Parkinson’s disease
Paul Marcogliese was studying to be a forensic scientist in Ottawa when he met local researcher David Park, a leading figure in studying neurodegenerative diseases. The two began a collaboration that nurtured in Marcogliese a personal and professional interest in Parkinson’s disease that has carried him to a major international research centre in the field.
After completing his doctorate in Park’s lab at the University of Ottawa, Marcogliese is now a postdoctoral associate in Hugo Bellen’s laboratory complex at the Baylor College of Medicine in Houston, Texas. The lab specializes in sophisticated studies on the humble fruit fly, whose genome is an ideal model for studying the genetic underpinnings of Parkinson’s.
Recent work in the Bellen lab has identified a role for fatty acids called ceramides in a rare form of Parkinson’s disease. Researchers observed that the levels of ceramides increase in fly and mouse neurons before the cells start to degenerate. When this happens in brain cells, various structures break down, including a crucial piece of a cell called the lysosome, which handles enzymes that normally digest waste products. Not being able to eliminate damaged portions of cells could limit the production of dopamine, the brain chemical that controls muscle movements in Parkinson’s disease. Marcogliese plans to examine whether known and new Parkinson’s disease genes are involved in regulating these ceramides.
“The goal is to leverage all of what we’ve learned from the flies and see if it can hold true in a mammalian system across multiple models,” explains Marcogliese, who is now broadening his studies to include mice. This work includes using drugs that can enhance the ability of brain cells to process ceramides, which may be a key mechanism for treating Parkinson’s disease patients.
Given early results in delivering drugs that resolve this problem in insect brains, Marcogliese hopes restoring this cell function could improve the lives of people with Parkinson’s.
“The question we’re now exploring is whether we can use these compounds to rescue this cell function in other species,” he says.
Identifying the genes responsible for the problem represents a step forward. Many new Parkinson’s disease genes are involved in ceramide processing at the cellular level. Marcogliese hopes that by checking the status of these genes or metabolic changes early on, an individual’s prospects for acquiring Parkinson’s could be identified earlier.
“We want to be able to diagnose patients 20 years before they get a tremor,” he says.
Diagnosing people before they show tremors, stiffness or rigidity would provide people with the opportunity for earlier treatment, possibly avoiding those symptoms altogether.