|29 January 2016|

A major breakthrough has been made in the fight against Parkinson’s disease.

An international public-private consortium of researchers brought together by the University of Dundee and led by The Michael J. Fox Foundation for Parkinson’s Research has identified and validated for the first time the cellular role of a primary Parkinson’s disease drug target.

In work published in eLife, the team comprising investigators from the University of Dundee, Max Planck Institute of Biochemistry, GlaxoSmithKline and MSD, known as Merck & Co., Inc., in the United States and Canada, has discovered that the LRRK2 kinase regulates cellular trafficking by deactivating Rab proteins.

Professor Dario Alessi, director of the Medical Research Council Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee, said the findings represented a major breakthrough in understanding the role of LRRK2 in causing Parkinson’s disease.

“The unique model of collaboration in this project and our systematic approach across laboratories using advanced technologies and layers of confirmation provide a firm foundation from which to continue this line of investigation and further refine our understanding of the LRRK2 Rab relationship.”

“The pathological cascade leading to brain diseases such as Parkinson’s likely includes many cellular players,” said Matthias Mann, PhD, Director of the Department of Proteomics and Signal Transduction at the Max Planck Institute of Biochemistry. “The identification of this LRRK2 substrate gives us a central piece in this puzzle and another potential place to intervene in the disease process.”

Marco Baptista, PhD, MJFF senior associate director of Research Programs, said: “Identification of Rab proteins as a LRRK2 substrate presents a tool to measure the impact of these inhibitors not only on LRRK2 levels but also on LRRK2 function. This critical component will advance development of these therapies to slow or stop Parkinson’s disease, patients’ greatest unmet need.”