Transcription factor EB agonists from natural products for treating human diseases with impaired autophagy-lysosome pathway

Abstract

Autophagy is a highly conserved degradation process for long-lived intracellular proteins and organelles mediated by lysosomes. Deficits in the autophagy-lysosome pathway (ALP) have been linked to a variety of human diseases, including neurodegenerative diseases, lysosomal storage disorders, and cancers. Transcription factor EB (TFEB) has been identified as a major regulator of autophagy and lysosomal biogenesis. Increasing evidence has demonstrated that TFEB activation can promote the clearance of toxic protein aggregates and regulate cellular metabolism. Traditional Chinese medicine (TCM)-derived natural products as important sources for drug discovery have been widely used for the treatment of various diseases associated with ALP dysfunction. Herein, we review (1) the regulation of TFEB and ALP; (2) TFEB and ALP dysregulation in human diseases; (3) TFEB activators from natural products and their potential uses.

Curcumin Derivative MTH-3 Regulates Palmitate-induced Insulin Resistance in Mouse Myoblast C2C12Cells

“…TFEB is a transcription factor, and acts as a primary regulator of autophagy, lysosomal genesis, lipid and energy metabolism, and the immune response (52)(53)(54)(55). Previous studies demonstrated that TFEB can advance neurodegenerative diseases, such as Parkinson's disease and Huntington's disease (56,57). TFEB also serves an important role in the metabolic response to starvation (58)(59)(60).…”

Autophagy and necroptosis in cisplatin-induced acute kidney injury: Recent advances regarding their role and therapeutic potential

“…Upon closure, mature Frontiers in Pharmacology frontiersin.org autophagosome engulfs the autophagic cargoes and subsequently fuses with lysosomes. Finally, the autophagic cargoes are metabolized by hydrolytic enzymes of lysosomes, and degraded contents are returned into the cytoplasm through lysosomal efflux permeases for reuse (Jing and Lim, 2012;Jin and Klionsky, 2014;Xu et al, 2020) (Figure 4).…”

Protective Effect of Natural Medicinal Plants on Cardiomyocyte Injury in Heart Failure: Targeting the Dysregulation of Mitochondrial Homeostasis and Mitophagy

“…TFEB is closely associated with lysosome synthesis, impaired autophagic degradation, poor fusion of autophagosomes and lysosomes, and lysosomal dysfunction. The regulation mechanisms by TFEB and lysosomes may be central to autophagy regulation [ 114 ]. Lysosomal biosynthesis is tightly controlled by the cellular metabolic state and by signaling from lysosomal membrane-bound molecules.…”