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Evaluating and modulating TFEB in the control of autophagy: toward new treatments in CNS disorders
Author(s) -
Costa Anaelle,
Metais Thibaud,
Mouthon Franck,
Kerkovich Danielle,
Charvériat Mathieu
Publication year - 2021
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12634
Subject(s) - tfeb , autophagy , microbiology and biotechnology , lysosome , biology , transcription factor , basic helix loop helix leucine zipper transcription factors , autophagosome , enzyme , gene , biochemistry , dna binding protein , apoptosis
TFEB is a mammalian transcription factor that binds directly to the CLEAR consensus sequence (5′‐GTCACGTGAC‐3′) present in the regulatory regions of genes inducing autophagosome formation, autophagosome‐lysosome fusion, hydrolase enzyme expression, and lysosomal exocytosis. By modulating these activities, TFEB coordinates on‐demand control over each cell’s degradation pathway. Thus, a nuclear signaling pathway regulates cellular energy metabolism through TFEB. Our growing understanding of the role of TFEB and CLEAR in the promotion of healthy clearance together with in vitro and in vivo preclinical findings in various animal models of disease supports the conclusion that the pharmacological activation of TFEB could clear toxic proteins to treat both rare and common forms of neurodegenerative disease.