Research Paper Volume 12, Issue 24 pp 25581—25598

A dual inhibitor targeting HMG-CoA reductase and histone deacetylase mitigates neurite degeneration in LRRK2-G2019S parkinsonism

class="figure-viewer-img"

Figure 7. Enhanced expression of acetyl-tubulin by JMF3086 promoted mitochondrial antegrade movement in the axons of SH-SY5Y cells carrying LRRK2-G2019S. Mitochondrial movement was labeled by mito-GFP in representative axons. (A) Kymographs depicting mitochondrial motility. A segment of axon was imaged continuously for 3 hours with a short break to allow for drug administration. Images were acquired at 10-second intervals. Left, SH-SY5Y control cells without treatment. Middle, LRRK2-G2019S cells without treatment. Right, LRRK2-G2019S cells treated with 0.5 μM JMF3086 for 24 hours. (B, C) From kymographs in (A), we determined and averaged the percentage of time that each mitochondrion was in motion in an antegrade direction to the terminal neurite (B) or retrograde to the soma (C). n = 30–50 mitochondria from nine axons per genotype and treatment. Data represent mean ± SD. *P<0.05, **P<0.01.