Proceedings of the National Academy of Sciences of the United States of America · 2022
Small molecule C381 targets the lysosome to reduce inflammation and ameliorate disease in models of neurodegeneration.
СтатьяНазвание и аннотация: Перевод в очереди
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Vest Ryan T, Chou Ching-Chieh, Zhang Hui, Haney Michael S, Li Lulin, Laqtom Nouf N, Chang Betty, Shuken Steven, Nguyen Andy, Yerra Lakshmi, Yang Andrew C, Green Carol, Tanga Mary, Abu-Remaileh Monther, Bassik Michael C, Frydman Judith, Luo Jian, Wyss-Coray Tony
Аннотация
SignificanceNeurodegenerative diseases are poorly understood and difficult to treat. One common hallmark is lysosomal dysfunction leading to the accumulation of aggregates and other undegradable materials, which cause damage to brain resident cells. Lysosomes are acidic organelles responsible for breaking down biomolecules and recycling their constitutive parts. In this work, we find that the antiinflammatory and neuroprotective compound, discovered via a phenotypic screen, imparts its beneficial effects by targeting the lysosome and restoring its function. This is established using a genome-wide CRISPRi target identification screen and then confirmed using a variety of lysosome-targeted studies. The resulting small molecule from this study represents a potential treatment for neurodegenerative diseases as well as a research tool for the study of lysosomes in disease.