Abstract
Ubiquitin signals play various roles in proteolytic and non-proteolytic functions. Ubiquitin signals are recognized as targets of the ubiquitin-proteasome system and the autophagy-lysosome pathway. In autophagy, ubiquitin signals are required for selective incorporation of cargoes, such as proteins, organelles, and microbial invaders, into autophagosomes. Autophagy receptors possessing an LC3-binding domain and a ubiquitin binding domain are involved in this process. Autophagy activity can decline as a result of genetic variation, aging, or lifestyle, resulting in the onset of various neurodegenerative diseases. This review summarizes the selective autophagy of neurodegenerative disease-associated protein aggregates via autophagy receptors and discusses its therapeutic application for neurodegenerative diseases.
Keywords:
autophagy; autophagy–lysosome pathway; neurodegenerative diseases; ubiquitin; ubiquitin–proteasome system.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Aging / genetics*
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Aging / metabolism
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Aging / pathology
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Alzheimer Disease / genetics*
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Alzheimer Disease / metabolism
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Alzheimer Disease / pathology
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Amyloid beta-Peptides / genetics
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Amyloid beta-Peptides / metabolism
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Amyotrophic Lateral Sclerosis / genetics*
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Amyotrophic Lateral Sclerosis / metabolism
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Amyotrophic Lateral Sclerosis / pathology
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Autophagy / genetics*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Gene Expression Regulation
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Humans
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Huntington Disease / genetics*
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Huntington Disease / metabolism
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Huntington Disease / pathology
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Lysosomes / metabolism
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / metabolism
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Parkinson Disease / genetics*
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Parkinson Disease / metabolism
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Parkinson Disease / pathology
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Proteasome Endopeptidase Complex / metabolism
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Proteolysis
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Sequestosome-1 Protein / genetics
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Sequestosome-1 Protein / metabolism
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Signal Transduction
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Ubiquitin / genetics*
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Ubiquitin / metabolism
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism
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Ubiquitination
Substances
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Amyloid beta-Peptides
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Cell Cycle Proteins
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Membrane Transport Proteins
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OPTN protein, human
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SQSTM1 protein, human
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Sequestosome-1 Protein
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Ubiquitin
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Ubiquitin-Protein Ligases
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parkin protein
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Proteasome Endopeptidase Complex