Give me a SINE: how Selective Inhibitors of Nuclear Export modulate autophagy and aging.
Give me a SINE: how Selective Inhibitors of Nuclear Export modulate autophagy and aging.
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DOI：
10.1080/23723556.2018.1502511
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发表时间：
2018
影响因子：
2.1
通讯作者：
Lapierre LR
中科院分区：
文献类型：
--
作者：
Kumar AV;Thakurta TG;Silvestrini MJ;Johnson JR;Reenan RA;Lapierre LR
自噬是一种细胞循环利用过程，会导致受损大分子在溶酶体中降解，这一过程可保护细胞免受衰老影响。转录因子EB（TFEB）是参与自噬和溶酶体功能相关基因的主要转录调节因子，正逐渐成为药物调控的一个有吸引力的靶点。最近，我们证实，通过RNA干扰或使用核输出选择性抑制剂（SINE）抑制核输出蛋白输出蛋白1（XPO1或CRM1）的功能，会导致TFEB在细胞核内富集，并增强模式生物和人类细胞中的自噬作用。除了目前为验证SINE在癌症治疗中的应用所做的努力之外，我们的研究还凸显了这些药物在改善神经退行性疾病和衰老相关病症方面的潜在益处。
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.