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Significance Amyotrophic lateral sclerosis is an adult-onset paralytic disorder whose mechanism remains uncertain. In this work, we report a defect in the retromer complex, which plays a crucial role in… Click to show full abstract
Significance Amyotrophic lateral sclerosis is an adult-onset paralytic disorder whose mechanism remains uncertain. In this work, we report a defect in the retromer complex, which plays a crucial role in endosomal protein sorting and trafficking in this fatal neurological disease. We found that restoring retromer expression in a mouse model of the disease aggravates the paralytic phenotype, whereas reducing retromer expression has the opposite beneficial effect. Our study sheds light on a role for retromer in neurodegeneration of pathogenic and therapeutic importance.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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