Many of the fatal neurodegenerative disorders that plague humankind, including Alzheimer's and Parkinson's disease, are connected with the misfolding of specific proteins into a surprisingly generic fibrous conformation termed amyloid. Prior to amyloid fiber assembly, many proteins populate a common oligomeric conformation, which may be severely cytotoxic. Therapeutic innovations are desperately sought to safely reverse this aberrant protein aggregation and return proteins to normal function. Whether mammalian cells possess any such endogenous activity remains unclear. By contrast, fungi, plants and bacteria all express Hsp104, a protein-remodeling factor, which synergizes with the Hsp70 chaperone system to resolve aggregated proteins and restore their functionality. Surprisingly, amyloids can also be adaptive. In yeast, Hsp104 directly regulates the amyloidogenesis of several prion proteins, which can confer selective advantages. Here, I review the modus operandi of Hsp104 and showcase efforts to unleash Hsp104 on the protein-misfolding events connected to disparate neurodegenerative amyloidoses.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.
Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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