Team Alessi

Study Rationale: Genetic mutations that lead to the activation of the enzyme LRRK2 are a major cause of inherited Parkinson’s disease. Team Alessi aims to combine the complementary expertise of its four research laboratories to perform fundamental, state-of-the-art experimentation to better comprehend the biology that is controlled by LRRK2. Team Alessi’s goal is to gain a much better understanding of LRRK2-driven Parkinson’s disease, hopefully providing a foundation for the development of future therapies.

Hypothesis: LRRK2 targets and modifies a set of enzymes known as Rab GTPases, triggering new biological events by creating new protein: protein interactions. Team Alessi aims to decipher what controls the activity of LRRK2 and to explore, in precise molecular detail, how this enzyme affects three major cellular structures (cilia, lysosomes, and mitochondria) implicated in Parkinson’s disease.

Study Design: Team Alessi showed that mutant LRRK2 triggers a series of molecular changes that cause new sets of proteins to interact. Team Alessi’s goal is to use a combination of state-of-the-art approaches to understand the consequences of these new interactions on the biology of three important subcellular compartments: primary cilia, lysosomes, and mitochondria.

Impact on Diagnosis/Treatment of Parkinson’s Disease: Team Alessi’s findings will provide novel, fundamental information of relevance to understanding the origin and progression of Parkinson’s that they hope will lead to new ideas to better diagnose, treat, and even prevent this malady in the future.