Give Me A Sine: How Selective Inhibitors Of Nuclear Export Modulate Autophagy And Aging

Autophagy is a cellular recycling process leading to lysosomal degradation of damaged macromolecules, which can protect cells against aging. The transcription factor EB (TFEB), a major transcriptional regulator of genes involved in autophagy and lysosomal function, is emerging as an attractive target for pharmacological modulation. Recently, we demonstrated that inhibiting the function of nuclear export protein exportin 1 (XPO1 or CRM1) with RNAi or with selective inhibitors of nuclear export (SINE) results in the nuclear enrichment of TFEB and enhancement of autophagy in model organisms and human cells. In addition to current efforts to validate the use of SINE in cancer therapies, our work highlights the potential benefits of these drugs toward improving outcomes in neurodegenerative diseases and aging.