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Age-related neurodegenerative disorders are characterized by the progressive accumulation of misfolded and aggregated proteins. SNARE protein ykt6 plays a crucial role in proteostasis and lysosomal function by enhancing hydrolase trafficking under stressful conditions. 

Activating ykt6 by small-molecule farnesyltransferase inhibitors (FTIs) restores lysosomal activity and reduces a-synuclein in patient-derived neurons and mice. Pharmacokinetic studies revealed that after a single oral dose, the FTI (LNK-754) was cleared from plasma within 20 hours and could rapidly cross the blood-brain-barrier. 

Pharmacokinetic analysis was performed as a service provided by Medicilon.

Reference

Leah K Cuddy, et al. Stress-Induced Cellular Clearance Is Mediated by the SNARE Protein ykt6 and Disrupted by α-Synuclein. Neuron. 2019 Dec 4;104(5):869-884.e11. doi: 10.1016/j.neuron.2019.09.001.