ArticleJournal of neuropathology and experimental neurology2018
Protein Phosphatase 2A and Its Methylation Modulating Enzymes LCMT-1 and PME-1 Are Dysregulated in Tauopathies of Progressive Supranuclear Palsy and Alzheimer Disease.
Article in Journal of neuropathology and experimental neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Pooled it
- Pharmacological Blocking of Adiponectin Receptors Induces Alzheimer's Disease-like Neuropathology and Impairs Hippocampal Function.Biomedicines · 2025Article
- Posttranslational Modifications ofPharmacological reviews · 2024Review
- LncRNA ENST00000440246.1 Promotes Alzheimer's Disease Progression by Targeting PP2A.Biochemical genetics · 2024Article
- Re-Arranging the Puzzle between the Amyloid-Beta and Tau Pathology: An APP-Centric Approach.International journal of molecular sciences · 2023Review
- Article
- Methyl donor supplementation reduces phospho-Tau, Fyn and demethylated protein phosphatase 2A levels and mitigates learning and motor deficits in a mouse model of tauopathy.Neuropathology and applied neurobiology · 2023Article
- PME-1 sensitizes glioblastoma cells to oxidative stress-induced cell death by attenuating PP2A-B55α-mediated inactivation of MAPKAPK2-RIPK1 signaling.Cell death discovery · 2023Article
- PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability.Brain : a journal of neurology · 2023Article
- Tau protein plays a role in the mechanism of cognitive disorders induced by anesthetic drugs.Frontiers in neuroscience · 2023Review
- Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer's models.Cell reports · 2022Article
- Tau Protein Modulates Perineuronal Extracellular Matrix Expression in the TauP301L-Biomolecules · 2022Article
- Protein phosphatase 2A restrains DLK signaling to promote proper Drosophila synaptic development and mammalian cortical neuron survival.Neurobiology of disease · 2022Article
- Review
- Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?International journal of molecular sciences · 2021Review
- Potential of Amantadine to Ameliorate Glutamate-Induced Pyramidal Cells Toxicity in Juvenile Rat' Brain Cortex.Neurotoxicity research · 2021Article
- Protein phosphatase 2A - structure, function and role in neurodevelopmental disorders.Journal of cell science · 2021Review
- The potential role of glial cells in driving the prion-like transcellular propagation of tau in tauopathies.Brain, behavior, & immunity - health · 2021Review
- Review of PP2A Tumor Biology and Antitumor Effects of PP2A Inhibitor LB100 in the Nervous System.Cancers · 2021Review
- Leucine Carboxyl Methyltransferase 1 Overexpression Protects Against Cognitive and Electrophysiological Impairments in Tg2576 APP Transgenic Mice.Journal of Alzheimer's disease : JAD · 2021Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Hyperphosphorylated tau aggregates are characteristic of tauopathies including progressive supranuclear palsy (PSP) and Alzheimer disease (AD), but factors contributing to pathologic tau phosphorylation are not well understood. Here, we studied the regulation of the major tau phosphatase, the heterotrimeric AB55αC protein phosphatase 2 A (PP2A), in PSP and AD. The assembly and activity of this PP2A isoform are regulated by reversible carboxyl methylation of its catalytic C subunit, while the B subunit confers substrate specificity. We sought to address whether the decreases in PP2A methylation and its methylating enzyme, leucine carboxyl methyltransferase (LCMT-1), which are reported in AD, relate to tau pathology or to concomitant amyloid pathology by comparing them in the relatively pure tauopathy PSP. Immunohistochemical analysis of frontal cortices showed that methyl-PP2A is reduced while demethyl-PP2A is increased, with no changes in total PP2A or B55α subunit, resulting in a reduction in the methyl/demethyl PP2A ratio of 63% in PSP and 75% in AD compared to controls. Similarly, Western blot analyses showed a decrease of methyl-PP2A and an increase of demethyl-PP2A with a concomitant reduction in the methyl/demethyl PP2A ratio in both PSP (74%) and AD (76%) brains. This was associated with a decrease in LCMT-1 and an increase in the demethylating enzyme, protein phosphatase methylesterase (PME-1), in both diseases. These findings suggest that PP2A dysregulation in tauopathies may contribute to the accumulation of hyperphosphorylated tau and to neurodegeneration.
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