LC3-mHTT-IN-1 is a mHTT-LC3 linker compound, which interacts with mutant huntingtin protein (mHTT) and LC3B but not with wtHTT or irrelevant control proteins.
Mutant huntingtin protein (mHTT) contains an expanded polyglutamine tract and causes Huntington’s disease (HD). Microtubule-associated proteins 1A/1B light chain 3B (LC3) is a protein associated with autophagy substrate selection and autophagosome biogenesis. mHTT can be degraded by autophagy, during which protein substrates are incorporated into autophagosomes associated with LC3. LC3-mHTT-IN-AN1 is a mHTT-LC3 linker compound that interacts with both mHTT and LC3, but not with wild-type HTT. LC3-mHTT-IN-AN1 at concentrations of 10 – 300nM reduced the level of mHTT in cultured HD mouse neurons in an allele-selective manner. LC3-mHTT-IN-AN1 also reduced the level of mutant but not wild-type ATXN3 in primary fibroblasts from patients with spinocerebellar ataxia type 3. Treatment with LC3-mHTT-IN-AN1 (2 μl at 25 μM per day) for 10 days led to a significant lowering of mHTT in the cortices of HD mice[1].
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