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2007 Grant - Wolozin

LRRK2 Interactions With Pathways Linked to Protein Folding and Degradation

Benjamin Wolozin, M.D., Ph.D.
Boston University
Boston, Massachusetts

2007 Investigator-Initiated Research Grant

Leucine-rich repeat kinase 2 (LRRK2) is a complex protein whose function is not well understood. But it is known that mutations in the gene providing a "blueprint" for LRRK2 protein production are the most common cause of inherited Parkinson's disease.

Benjami Wolozin, M.D., Ph.D., and colleagues have been studying the functions of the LRRK2 protein in a simple animal model (the roundworm C. elegans), as well as in cultured cell lines and nerve cells. They have shown that the normal LRRK2 protein protects cells against oxidative damage (damage from normally occurring toxic oxygen molecules). When the LRRK2 gene carries a Parkinson-related mutation, the protein appears to lose its protective function, and a cell is susceptible to oxidative damage.

The researchers have initial results suggesting that the protective effect of normal LRRK2 requires interaction with the machinery inside the cell that folds proteins into their correct shape.

The researchers plan to study in more detail how the LRRK2 protein interacts with parts of the cell involved in protein folding. They also plan to study how the LRRK2 protein protects cells against oxidative damage. Finally, they will study how the LRRK2 protein interacts with proteins that have been implicated in the pathology of Alzheimer's disease. Their studies will provide greater understanding of how normal cells are protected against damage and how cells become damaged in diseases such as Parkinson's disease and Alzheimer's disease.