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Ann N Y Acad Sci. 2016 May;1371(1):3-14. doi: 10.1111/nyas.13131.

Transcription factor EB: from master coordinator of lysosomal pathways to candidate therapeutic target in degenerative storage diseases.

Author information

1
Department of Molecular and Human Genetics, Baylor College of Medicine, and Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas.

Abstract

The lysosome is the main catabolic hub of the cell. Owing to its role in fundamental processes such as autophagy, plasma membrane repair, mTOR signaling, and maintenance of cellular homeostasis, the lysosome has a profound influence on cellular metabolism and human health. Indeed, inefficient or impaired lysosomal function has been implicated in the pathogenesis of a number of degenerative diseases affecting various organs and tissues, most notably the brain, liver, and muscle. The discovery of the coordinated lysosomal expression and regulation (CLEAR) genetic program and its master controller, transcription factor EB (TFEB), has provided an unprecedented tool to study and manipulate lysosomal function. Most lysosome-based processes-including macromolecule degradation, autophagy, lysosomal exocytosis, and proteostasis-are under the transcriptional control of TFEB. Interestingly, impaired TFEB signaling has been suggested to be a contributing factor in the pathogenesis of several degenerative storage diseases. Preclinical studies based on TFEB exogenous expression to reinstate TFEB activity or promote CLEAR network-based lysosomal enhancement have highlighted TFEB as a candidate therapeutic target for the treatment of various degenerative storage diseases.

KEYWORDS:

TFEB; autophagy; degenerative storage diseases; degradative pathways; lysosome enhancement; proteinopathies; transcription factor EB

PMID:
27299292
PMCID:
PMC5032832
DOI:
10.1111/nyas.13131
[Indexed for MEDLINE]
Free PMC Article

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