What is g2019s-lrrk2?
LRRK2 can be chronically and fully inhibited without reducing total LRRK2 levels. G2019S-LRRK2 is resilient to inhibition and blocks inhibitor induced phenotypes. The G2019S mutation in LRRK2 is one of the most common known genetic causes of neurodegeneration and Parkinson disease (PD).
What is The G2019S mutation?
The G2019S mutation is the most common mutation, with an incidence up to 40% in specific populations 2, 3, and often presents with alpha-synuclein (aSyn) Lewy neuropathology 4, apart from Tau pathology 5. Leucine-Rich Repeat Kinase 2 (LRRK2) is a large multidomain protein with GTPase and kinase domains in close vicinity 6.
What is the global prevalence of G2019S?
However, the prevalence of G2019S is population specific: very rare in Asia, 15 low in Northern Europe, 8 and high in Italy, 12 Spain 16 and Portugal. 17 Haplotype analyses revealed that all carriers of this mutation inherited the same ancestral chromosome. 8, 12, 18
What can we learn from g2019s-lrrk2?
Fig. 1: G2019S-LRRK2 cells selectively accumulate intracellular pS129-aSyn inclusions and display LC3 accumulation. Fig. 2: Lysosomal morphology and proteolytic activity are altered in G2019S-LRRK2 cells. Fig. 3: The velocity of the autophagic flux is unchanged in LRRK2 cells.
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