Study found that autophagy can be stimulated by inhibiting XPO1 protein expression

Copyright © iCell Bioscience Inc, Shanghai 2018-2019

Autophagy is the process by which a cell rebuilds itself by recovering its own cellular proteins or by abrading organelles. In this process, cells phagocytose these proteins or organelles and entrap them in vesicles called autophagosomes, which fuse with lysosomes to form autolysosomes, degrade them and encapsulate them. The contents, to achieve cell metabolism and the renewal of certain organelles. Studies have shown that many age-related diseases, including neurodegenerative diseases, are associated with cellular autophagy dysfunction.

Researchers at Brown University in the United States have found a new strategy for stimulating cell autophagy—stimulating cell autophagy by inhibiting the expression of a protein called XPO1. This strategy can be used in the future to treat Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and other age-related neurodegenerative diseases.

The team found that inhibition of XPO1 expression in Caenorhabditis elegans will increase the level of autophagic transcription factors in the nucleus, leading to an increase in autophagosomes, lysosomes, and autolysosomes, stimulating autophagy, which is significant. Increase nematode life. And a cancer drug, selective nuclear export inhibitor (SINE), can be used as a drug that inhibits XPO1 and implements a cell autophagy strategy.

Drosophila experiments show that SINE can prolong the lifespan of fruit fly infected with ALS. Human cell experiments showed that the effect of XPO1 inhibitors on autophagy in human cells was similar to that of nematodes. In SINE-treated human HeLa cells, the level of autophagic transcription factors in the nucleus also increases, and markers of autophagic activity such as autophagosomes and lysosomes increase.

The researchers said that XPO1 inhibitors can stimulate autophagy in human cells, but the current study can only prove that this strategy can be used as a potential means to increase autophagy and treatment of age-related diseases, in the future they will pass more neurodegenerative disease models Test these drugs.