ReviewMolecular biology of the cell2016
Engineering therapeutic protein disaggregases.
Review in Molecular biology of the cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed.
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- The mechanobiology of biomolecular condensates.Biophysics reviews · 2025Review
- Design principles to tailor Hsp104 therapeutics.Cell reports · 2024Article
- Tuning Hsp104 specificity to selectively detoxify α-synuclein.Molecular cell · 2023Article
- Limbic-predominant age-related TDP43 encephalopathy (LATE) neuropathological change in neurodegenerative diseases.Nature reviews. Neurology · 2023Review
- Regulating Phase Transition in Neurodegenerative Diseases by Nuclear Import Receptors.Biology · 2022Review
- Nuclear-Import Receptors Counter Deleterious Phase Transitions in Neurodegenerative Disease.Journal of molecular biology · 2022Review
- Prion-like proteins: from computational approaches to proteome-wide analysis.FEBS open bio · 2021Review
- FUS and TDP-43 Phases in Health and Disease.Trends in biochemical sciences · 2021Review
- The Cryo-EM Effect: Structural Biology of Neurodegenerative Disease Proteostasis Factors.Journal of neuropathology and experimental neurology · 2021Review
- (Dis)Solving the problem of aberrant protein states.Disease models & mechanisms · 2021Review
- Role and therapeutic potential of liquid-liquid phase separation in amyotrophic lateral sclerosis.Journal of molecular cell biology · 2021Review
- Combating deleterious phase transitions in neurodegenerative disease.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Illuminating amyloid fibrils: Fluorescence-based single-molecule approaches.Computational and structural biotechnology journal · 2021Review
- Structural and mechanistic insights into Hsp104 function revealed by synchrotron X-ray footprinting.The Journal of biological chemistry · 2020Article
- Augmentation of Bri2 molecular chaperone activity against amyloid-β reduces neurotoxicity in mouse hippocampus in vitro.Communications biology · 2020Article
- FAIM Opposes Aggregation of Mutant SOD1 That Typifies Some Forms of Familial Amyotrophic Lateral Sclerosis.Frontiers in neuroscience · 2020Article
- Yeast Models for Amyloids and Prions: Environmental Modulation and Drug Discovery.Molecules (Basel, Switzerland) · 2019Review
- Cellular stress leads to the formation of membraneless stress assemblies in eukaryotic cells.Traffic (Copenhagen, Denmark) · 2019Review
- Spiraling in Control: Structures and Mechanisms of the Hsp104 Disaggregase.Cold Spring Harbor perspectives in biology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
Abstract
Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD.
Indexed as
Identifiers
What OpenQuestion holds
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.