title: The Autophagy-Lysosomal Pathway in Neurodegeneration: A TFEB Perspective.
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.
authors.affiliation: 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.
authors.forename: Heidi
authors.initials: H
authors.lastname: Martini-Stoica
authors.affiliation: Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ballabio
authors.affiliation: 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.
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000502:physiology*; D001921:Brain / Q000503:physiopathology*; D006801:Humans; D008247:Lysosomes / Q000502:physiology*; D009410:Nerve Degeneration / Q000503:physiopathology*; D019636:Neurodegenerative Diseases / Q000503:physiopathology*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C064972:TFEB protein, human
keywords: TFEB; autophagy–lysosomal pathway; neurodegenerative disease; prion disease