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Discovery reveals how Parkinson’s-linked gene protects the brain


April 5, 2023

Members of the Schlossmacher team include (from left to right) Jacqueline Tokarew, Bojan Shutinoski, Julianna Tomlinson, Angela Nguyen, Michael Schlossmacher, Daniel El-Kodsi and Nathalie Lengacher. Other key contributors to the discovery missing from the photo include Qiubo Jiang, Juan Li, Ajanta Chatterji, Travis Fehr, Chris Kennedy and Chet HoltermanFor more than 20 years, researchers have known that young-onset Parkinson’s disease is often caused by mutations in the parkin gene, but the exact function of this gene has been hotly debated.

Researchers at The Ottawa Hospital and uOttawa recently made a major contribution to this debate with their study showing that parkin acts like a powerful antioxidant that disarms potentially harmful oxidants in the brain.

Their follow-up study, published in Acta Neuropathologica Communications, reveals that parkin’s antioxidant activity involves glutathione – a natural substance produced in almost all cells.

Using animal, cell and biochemical models, the team showed that parkin could recycle a ‘used-up form’ of glutathione into a helpful antioxidant version. In parkin’s absence, cells try to produce more of the antioxidant version of glutathione, but that doesn’t replace all of parkin’s protective effects.

The results could lead to new treatments for Parkinson’s disease, as well as innovative glutathione-based approaches to monitor disease progression.

“Seeing this extensive body of work come to fruition only reinvigorates my passion for Parkinson disease research and encourages me to keep contributing to the field, on behalf of all PD patients and their families,” said lead author Dr. Daniel El Kodsi.“Seeing this extensive body of work come to fruition only reinvigorates my passion for Parkinson disease research and encourages me to keep contributing to the field, on behalf of all PD patients and their families,” said lead author Dr. Daniel El Kodsi, former postdoctoral fellow at The Ottawa Hospital and currently Research Scientist and Program Manager at Brigham and Women's Hospital and Harvard Medical School. “Under the mentorship of Dr. Michael G. Schlossmacher I learned a lot and cultivated many skills, but most of all I was inspired to not be afraid to challenge the field in the pursuit of the truth in science.”

Authors: El Kodsi DN, Tokarew JM, Sengupta R, Lengacher NA, Chatterji A, Nguyen AP, Boston H, Jiang Q, Palmberg C, Pileggi C, Holterman CE, Shutinoski B, Li J, Fehr TK, LaVoie MJ, Ratan RR, Shaw GS, Takanashi M, Hattori N, Kennedy CR, Harper ME, Holmgren A, and co-corresponding authors Tomlinson JJ and Schlossmacher MG.

Funders: Canadian Institutes of Health Research, Canada Research Chair Program, Michael J. Fox Foundation for Parkinson’s Research, National Institutes of Health, Parkinson Research Consortium of Ottawa, Queen Elizabeth II Graduate Scholarship Fund, Uttra and Sam Bhargava Family, Department of Medicine at The Ottawa Hospital and Faculty of Medicine. All research at The Ottawa Hospital is also enabled by generous donors to The Ottawa Hospital Foundation.

The Ottawa Hospital is a leading academic health, research and learning hospital proudly affiliated with the University of Ottawa and supported by The Ottawa Hospital Foundation.

 

Disease and research area tags: Brain and neuromuscular disease, Parkinson's

Scientific Program tags: Neuroscience Program