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June 22, 2021
Protein phosphatase 2A holoenzymes regulate leucine-rich repeat kinase 2 phosphorylation and accumulation.
(PubMed, Neurobiol Dis)
- "Dephosphorylation at LRRK2's S910/S935/S955/S973 phosphosite cluster is observed in several conditions including in sporadic PD brain, in several disease mutant forms of LRRK2 and after pharmacological LRRK2 kinase inhibition...Furthermore, we demonstrated that this specific PP2A holoenzyme induces LRRK2 relocalization and triggers LRRK2 ubiquitination, suggesting its involvement in LRRK2 clearance. The identification of the PPP2CA:PPP2R2 complex regulating LRRK2 S910/S935/S955/S973 phosphorylation paves the way for studies refining PD therapeutic strategies that impact LRRK2 phosphorylation."
Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • Targeted Protein Degradation • GNRP • PPP2CA • RASGRF1
April 10, 2021
Differential Inhibition of LRRK2 in Parkinson’s Disease Patient Blood by a G2019S Selective LRRK2 Inhibitor.
(PubMed, Mov Disord)
- "These findings demonstrate that EB-42168, a G2019S LRRK2 selective inhibitor, lowers mutant G2019S LRRK2 phosphorylated biomarkers while simultaneously sparing WT LRRK2. Selective targeting of G2019S LRRK2 with a small molecule lays the foundation for a precision medicine treatment of G2019S LRRK2 PD."
Journal • Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease
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