A5047950628- Parkinson's Disease Mechanisms and Treatments
- biodegradable polymer synthesis and properties
- Cellular transport and secretion
- Nuclear Receptors and Signaling
- Lysosomal Storage Disorders Research
Harvard University
2021-2022
Brigham and Women's Hospital
2021-2022
Significance The mechanisms responsible for brain α-synuclein (αS) dyshomeostasis, caused by Gaucher’s GBA1 mutations that increase Parkinson’s disease (PD) risk, are largely unknown. We previously showed abrogating physiological αS tetramers a familial PD-E46K–amplified 3K mutation produces PD-like syndrome in mice and treatment with stearoyl-CoA desaturase inhibitors increased portion of the tetramers, benefitting motor phenotypes. Here, we show that—similar to previous findings...
Increasing evidence has shown that Parkinson's disease (PD) impairs midbrain dopaminergic, cortical and other neuronal subtypes in large part due to the build-up of lipid- vesicle-rich α-synuclein (αSyn) cytotoxic inclusions. We previously identified stearoyl-CoA desaturase (SCD) as a potential therapeutic target for synucleinopathies. A brain-penetrant SCD inhibitor, YTX-7739, was developed entered Phase 1 clinical trials. Here, we report efficacy YTX-7739 reversing pathological αSyn...