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Trends Neurosci. 2016 Apr;39(4):221-234. doi: 10.1016/j.tins.2016.02.002. Epub 2016 Mar 9.

The Autophagy-Lysosomal Pathway in Neurodegeneration: A TFEB Perspective.

Author information

1
Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA; Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA.
2
Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA.
3
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Dan and Jan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA; Telethon Institute of Genetics and Medicine (TIGEM) and Department of Translational Medical Sciences, Frederico II University, Naples, Italy.
4
Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX. Electronic address: huiz@bcm.edu.

Abstract

The autophagy-lysosomal pathway (ALP) is involved in the degradation of long-lived proteins. Deficits in the ALP result in protein aggregation, the generation of toxic protein species, and accumulation of dysfunctional organelles, which are hallmarks of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and prion disease. Decades of research have therefore focused on enhancing the ALP in neurodegenerative diseases. More recently, transcription factor EB (TFEB), a major regulator of autophagy and lysosomal biogenesis, has emerged as a leading factor in addressing disease pathology. We review the regulation of the ALP and TFEB and their impact on neurodegenerative diseases. We also offer our perspective on the complex role of autophagy and TFEB in disease pathogenesis and its therapeutic implications through the examination of prion disease.

KEYWORDS:

TFEB; autophagy–lysosomal pathway; neurodegenerative disease; prion disease

PMID:
26968346
PMCID:
PMC4928589
DOI:
10.1016/j.tins.2016.02.002
[Indexed for MEDLINE]
Free PMC Article

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