ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience1997
Selective destruction of stable microtubules and axons by inhibitors of protein serine/threonine phosphatases in cultured human neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 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
55 citing papers in PubMed, 141 citations in OpenAlex.
- Tau and neuroinflammation in Alzheimer's disease: interplay mechanisms and clinical translation.Journal of neuroinflammation · 2023Review
- Review
- Protein phosphatase 2A restrains DLK signaling to promote proper Drosophila synaptic development and mammalian cortical neuron survival.Neurobiology of disease · 2022Article
- Regulation of PP2A, PP4, and PP6 holoenzyme assembly by carboxyl-terminal methylation.Scientific reports · 2021Article
- AMPK Ameliorates Tau Acetylation and Memory Impairment Through Sirt1.Molecular neurobiology · 2020Article
- Effects of carboxyl-terminal methylation on holoenzyme function of the PP2A subfamily.Biochemical Society transactions · 2020Review
- Compound screening in cell-based models of tau inclusion formation: Comparison of primary neuron and HEK293 cell assays.The Journal of biological chemistry · 2020Article
- Targeting Tau to Treat Clinical Features of Huntington's Disease.Frontiers in neurology · 2020Review
- A brain-penetrant triazolopyrimidine enhances microtubule-stability, reduces axonal dysfunction and decreases tau pathology in a mouse tauopathy model.Molecular neurodegeneration · 2018Article
- Therapeutic strategies for the treatment of tauopathies: Hopes and challenges.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2016Review
- Evaluation of the brain-penetrant microtubule-stabilizing agent, dictyostatin, in the PS19 tau transgenic mouse model of tauopathy.Acta neuropathologica communications · 2016Article
- α-Synuclein Fibrils Exhibit Gain of Toxic Function, Promoting Tau Aggregation and Inhibiting Microtubule Assembly.The Journal of biological chemistry · 2016Article
- Characterization of Brain-Penetrant Pyrimidine-Containing Molecules with Differential Microtubule-Stabilizing Activities Developed as Potential Therapeutic Agents for Alzheimer's Disease and Related Tauopathies.The Journal of pharmacology and experimental therapeutics · 2016Article
- A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats.Acta pharmacologica Sinica · 2016Article
- The N-terminal Set-β Protein Isoform Induces Neuronal Death.The Journal of biological chemistry · 2015Article
- Microtubule-stabilizing agents as potential therapeutics for neurodegenerative disease.Bioorganic & medicinal chemistry · 2014Review
- Okadaic acid: more than a diarrheic toxin.Marine drugs · 2013Review
- PP2A regulatory subunit Bα controls endothelial contractility and vessel lumen integrity via regulation of HDAC7.The EMBO journal · 2013Article
- Brain-penetrant microtubule-stabilizing compounds as potential therapeutic agents for tauopathies.Biochemical Society transactions · 2012Review
- Inhibition of JNK by a peptide inhibitor reduces traumatic brain injury-induced tauopathy in transgenic mice.Journal of neuropathology and experimental neurology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Paired helical filaments (PHFs) in the neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) brains are composed of highly phosphorylated isoforms of tau (PHFtau) that fail to bind microtubules (MTs), and the levels of MT-binding competent tau are decreased in AD brains with abundant PHFtau. Because this loss of MT binding could compromise the viability of tangle-bearing AD neurons by destabilizing MTs, we asked whether these events could be initiated by inhibiting protein phosphatase 1 (PP1) and PP2A in cultured human neurons (NT2N cells) using okadaic acid (OK) and calyculin-A (CL-A). The treatment of NT2N cells with OK and CL-A increased tau phosphorylation, decreased the binding of tau to MTs, and selectively depolymerized the more stable detyrosinated MTs but not the more labile tyrosinated MTs. Significantly, this led to the rapid degeneration of axons, which are enriched in the more stable detyrosinated MTs, and PP2A was implicated in the initiation of this cascade of events because PP2A but not PP1 was closely associated with MTs in the NT2N cells. These studies imply that inactivation of PP2A in vulnerable neurons of the AD brain may play a mechanistic role in the conversion of normal tau into PHFtau, in the depolymerization of stable MTs, and in the degeneration of axons emanating from tangle-bearing neurons.
Indexed as
Identifiers
9221771PMC6573204W1674770932What 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.