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Analysis of the LRRK2-Rab Signaling Pathway

This grant builds upon the research from a prior grant: Rab Detection Initiative

Promising Outcomes of Original Grant:
The highlight of our teams' recent MJFF funded research has been the discovery of the key physiological targets of LRRK2 that comprise a group of proteins termed Rabs. We have exploited these findings to work with the MJFF to develop new antibody-based methods to interrogate LRRK2-signaling pathway in human derived blood cells. We have also discovered that two other proteins linked to Parkinson's, Rab29 and VPS35, work to control the activity of LRRK2.

Objectives for Supplemental Investigation:
There is still a lot of important work to do on this project that includes better understanding of how Rab29 and VPS35 control LRRK2 activity. We also wish to explore how Rab proteins targeted by LRRK2 are linked to Parkinson's. We aim to continue developing improved methods to assess LRRK2-targeted Rab proteins that are likely to comprise important biomarkers for assessing biology that is related to Parkinson's disease.

Importance of This Research for the Development of a New PD Therapy:
The research will provide fundamental knowledge on how important components of relevance to understanding Parkinson's are controlled, and could facilitate new approaches to better Parkinson's treatments. For example, screening for drugs that prevent Rab29 or VPS35 from activating LRRK2. The technology we are developing could assist clinicians with identifying patients that are most likely to benefit from a future LRRK2 inhibitor treatment.


  • Dario Alessi, PhD

    Dundee United Kingdom

  • Suzanne R. Pfeffer, PhD

    Stanford, CA United States

  • Matthias Mann, PhD

    Martinsried Germany

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