TFEB 在溶酶体功能障碍相关疾病中的作用。

Role of TFEB in Diseases Associated with Lysosomal Dysfunction.

机构信息

School of Optometry, Indiana University, Bloomington, IN, USA.

出版信息

Adv Exp Med Biol. 2023;1415:319-325. doi: 10.1007/978-3-031-27681-1_46.

Abstract

Transcription factor EB (TFEB) plays a very important role in the maintenance of cellular homeostasis. TFEB is a transcription factor that regulates the expression of several genes in the Coordinated Lysosomal Expression and Regulation (CLEAR) network. The CLEAR network genes are known to regulate many processes associated with the autophagy pathway and lysosome biogenesis. Lysosomes, which are degradative organelles in the cell, are associated with several cellular mechanisms, such as autophagy and phagocytosis. Recent studies have shown that TFEB dysregulation and lysosomal dysfunction are associated with several degenerative diseases. Thus, enhancing TFEB activity and accompanied induction of lysosomal function and autophagy can have tremendous therapeutic potential for the treatment of several degenerative diseases including age-related macular degeneration (AMD). In this chapter, we briefly illustrate the expression and regulation of TFEB in response to several cellular stressors and discuss the effects of TFEB overexpression to induce cellular clearance functions.

摘要

转录因子 EB（TFEB）在维持细胞内稳态方面起着非常重要的作用。TFEB 是一种转录因子，可调节协调溶酶体表达和调节（CLEAR）网络中几个基因的表达。已知 CLEAR 网络基因可调节与自噬途径和溶酶体发生相关的许多过程。溶酶体是细胞内的一种降解细胞器，与自噬和吞噬等多种细胞机制有关。最近的研究表明，TFEB 失调和溶酶体功能障碍与几种退行性疾病有关。因此，增强 TFEB 的活性并伴随诱导溶酶体功能和自噬，对于治疗包括年龄相关性黄斑变性（AMD）在内的几种退行性疾病具有巨大的治疗潜力。在本章中，我们简要说明了 TFEB 的表达和调节，以响应几种细胞应激，并讨论了过表达 TFEB 诱导细胞清除功能的影响。