The most frequent missense mutations in familial Parkinson’s disease (PD) occur in the highly conserved LRRK2/PARK8 gene with G2019S mutation. We previously established a fly model of PD carrying the LRRK2-G2019S mutation that exhibited the parkinsonism-like phenotypes. An herbal medicine, Gastrodia elata Blume (GE), has been reported to have neuroprotective effects in toxin-induced PD models. However, the underpinning molecular mechanisms of GE beneficiary to G2019S-induced PD remain unclear.

LRRK2 activity regulates the phosphorylation of a subset of Rab proteins, and Rab phosphorylation on lysosomes can be modulated in response to variants in PD-linked proteins and lysosomal damage.  In addition to sensing lysosomal damage, LRRK2 can also promote lysosomal dysfunction, leading to reduced GCase activity and alterations in BMP.  Using cellular and rodent models and PD patient samples, we explored the mechanisms by which LRRK2 regulates BMP and its functional significance with respect to GSL metabolism and disea

Warren will describe his experience of LRRK2 research and drug development from the perspective of biopharma.  The challenges, innovation, ups and downs will be presented from the early days of trying to figure out how to screen to the current clinical trials, which present their own hurdles.

Zoom registration link:  https://stanford.zoom.us/meeting/register/tJMsf-6tqj8jHNZ2L-V6sOCciWE1KzsPPhjs

Zoom link: https://stanford.zoom.us/meeting/register/tJMsf-6tqj8jHNZ2L-V6sOCciWE1KzsPPhjs

Zoom link: https://stanford.zoom.us/meeting/register/tJMsf-6tqj8jHNZ2L-V6sOCciWE1KzsPPhjs