ArticleHuman molecular genetics2015
The active Hsc70/tau complex can be exploited to enhance tau turnover without damaging microtubule dynamics.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 36 citations in OpenAlex.
- Neuroinflammation and Tauopathies.Molecular biology reports · 2026Review
- Synaptic Chaperone Dysfunction as a Convergent Mechanism in Neurodegenerative and Psychiatric Disorders.Neuroscience insights · 2026Review
- A novel lncRNA FAM151B-DT regulates degradation of aggregation prone proteins.Molecular psychiatry · 2025Article
- Design of multi-target peptide modulators for protein chaperone networks.Structure (London, England : 1993) · 2025Article
- DnaJs are enriched in tau regulators.International journal of biological macromolecules · 2023Article
- Article
- Hsc70-4 aggravates PolyQ-mediated neurodegeneration by modulating NF-κB mediated immune response inFrontiers in molecular neuroscience · 2022Article
- The Hidden Side of NCAM Family: NCAM2, a Key Cytoskeleton Organization Molecule Regulating Multiple Neural Functions.International journal of molecular sciences · 2021Review
- Article
- Mutant Ataxin-3-Containing Aggregates (MATAGGs) in Spinocerebellar Ataxia Type 3: Dynamics of the Disorder.Molecular neurobiology · 2021Review
- Inhibitors of heat shock protein 70 (Hsp70) with enhanced metabolic stability reduce tau levels.Bioorganic & medicinal chemistry letters · 2021Article
- Knockin' on heaven's door: Molecular mechanisms of neuronal tau uptake.Journal of neurochemistry · 2021Review
- Aberrant AZIN2 and polyamine metabolism precipitates tau neuropathology.The Journal of clinical investigation · 2021Article
- C-terminus of Hsp70 Interacting Protein (CHIP) and Neurodegeneration: Lessons from the Bench and Bedside.Current neuropharmacology · 2021Review
- Article
- Article
- Arginine π-stacking drives binding to fibrils of the Alzheimer protein Tau.Nature communications · 2020Article
- A unique tau conformation generated by an acetylation-mimic substitution modulates P301S-dependent tau pathology and hyperphosphorylation.The Journal of biological chemistry · 2019Article
- HspB1 and Hsc70 chaperones engage distinct tau species and have different inhibitory effects on amyloid formation.The Journal of biological chemistry · 2018Article
- Therapeutic Strategies for Restoring Tau Homeostasis.Cold Spring Harbor perspectives in medicine · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
The pathological accumulation of abnormally hyperphosphorylated and aggregated tau, a neuronal microtubule (MT)-associated protein that functions to maintain MT stability, is implicated in a number of hereditary and sporadic neurodegenerative diseases including frontotemporal dementia and Alzheimer's disease. Targeting tau for the treatment of these diseases is an area of intense interest and toward that end, modulation of cellular molecular chaperones is a potential therapeutic target. In particular, the constitutive Hsp70 isoform, Hsc70, seems highly interconnected with tau, preserving tau protein levels and synergizing with it to assemble MTs. But the relationship between tau and Hsc70, as well as the impact of this interaction in neurons and its therapeutic implications remain unknown. Using a human dominant negative Hsc70 that resembles isoform selective inhibition of this important chaperone, we found for the first time that Hsc70 activity is required to stimulate MT assembly in cells and brain. However, surprisingly, active Hsc70 also requires active tau to regulate MT assembly in vivo, suggesting that tau acts in some ways as a co-chaperone for Hsc70 to coordinate MT assembly. This was despite tau binding to Hsc70 as substrate, as determined biochemically. Moreover, we show that while chronic Hsc70 inhibition damaged MT dynamics, intermittent treatment with a small molecule Hsp70 inhibitor lowered tau in brain tissue without disrupting MT integrity. Thus, in tauopathies, where MT injury would be detrimental to neurons, the unique relationship of tau with the Hsc70 machinery can be exploited to deplete tau levels without damaging MT networks.
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.