ArticleJournal of experimental neuroscience2018
Could a Common Mechanism of Protein Degradation Impairment Underlie Many Neurodegenerative Diseases?
Article in Journal of experimental neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Exploring the ER channel protein Sec61: recent advances in pathophysiological significance and novel pharmacological inhibitors.Frontiers in pharmacology · 2025Review
- Pharmacologically increasing cGMP improves proteostasis and reduces neuropathy in mouse models of CMT1.Cellular and molecular life sciences : CMLS · 2024Article
- Effects of heterologous human tau protein expression in yeast models of proteotoxic stress response.CNS neuroscience & therapeutics · 2024Article
- Article
- Allosteric regulation of the 20S proteasome by the Catalytic Core Regulators (CCRs) family.Nature communications · 2023Article
- Raising cGMP restores proteasome function and myelination in mice with a proteotoxic neuropathy.Brain : a journal of neurology · 2022Article
- Activation of the ubiquitin-proteasome system contributes to oculopharyngeal muscular dystrophy through muscle atrophy.PLoS genetics · 2022Article
- Advances in Proteasome Enhancement by Small Molecules.Biomolecules · 2021Review
- Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway.International journal of molecular sciences · 2021Review
- Membrane Interactions Accelerate the Self-Aggregation of Huntingtin Exon 1 Fragments in a Polyglutamine Length-Dependent Manner.International journal of molecular sciences · 2021Article
- Common Factors in Neurodegeneration: A Meta-Study Revealing Shared Patterns on a Multi-Omics Scale.Cells · 2020Article
- From Seeds to Fibrils and Back: Fragmentation as an Overlooked Step in the Propagation of Prions and Prion-Like Proteins.Biomolecules · 2020Review
- Increased Dynamics of α-Synuclein Fibrils by β-Synuclein Leads to Reduced Seeding and Cytotoxicity.Scientific reports · 2019Article
- Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules.Molecules (Basel, Switzerland) · 2019Review
- Protein Misfolding and ER Stress in Huntington's Disease.Frontiers in molecular biosciences · 2019Review
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
At the cellular level, many neurodegenerative diseases (NDs), often considered proteinopathies, are characterized by the accumulation of misfolded and damaged proteins into large insoluble aggregates. Prominent species that accumulate early and play fundamental roles in disease pathogenesis are amyloid β (Aβ) and tau in Alzheimer disease, α-synuclein (α-syn) in Parkinson disease, and polyQ-expanded huntingtin (Htt) in Huntington disease. Although significant efforts have focused on how the cell deals with these protein aggregates, why is it that these misfolded proteins are not degraded normally in the first place? A vast body of literature supports the notion that the cell's protein degradation system for individual proteins-the ubiquitin proteasome system (UPS)-does not function sufficiently in many NDs. The proteasome itself has received significant focus for years due to its obvious failure to degrade misfolded proteins in ND, but no general mechanism has been uncovered. We have recently found that specific pathologically relevant oligomers can potently and directly inhibit the proteasome. What is most interesting is that the misfolded protein's primary amino acid sequence was irrelevant to its ability to inhibit. Instead, the culprit is the 3-dimensional shape of the misfolded oligomers. It turns out that many misfolded proteins in ND can take on this proteasome-impairing shape suggesting that there could be a common mechanism for UPS impairment in many NDs. The proteasome is already an important target for treating cancer, could it also be targeted to broadly treat ND?
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.