Evidence map›Paper›PMID 25202269›Full record

ArticleFrontiers in aging neuroscience2014

Altered protein phosphatase 2A methylation and Tau phosphorylation in the young and aged brain of methylenetetrahydrofolate reductase (MTHFR) deficient mice.

Jean-Marie Sontag, Brandi Wasek, Goce Taleski, Josephine Smith, Erland Arning, Estelle Sontag, Teodoro Bottiglieri

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in aging neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.8field-weighted citation impact, top 7% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 44 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Jean-Marie SontagSchool of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute Callaghan, NSW, Australia.
Brandi WasekInstitute of Metabolic Disease and Baylor Research Institute, Baylor University Medical Center Dallas, TX, USA.
Goce TaleskiSchool of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute Callaghan, NSW, Australia.
Josephine SmithSchool of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute Callaghan, NSW, Australia.
Erland ArningInstitute of Metabolic Disease and Baylor Research Institute, Baylor University Medical Center Dallas, TX, USA.
Estelle SontagSchool of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute Callaghan, NSW, Australia.
Teodoro BottiglieriInstitute of Metabolic Disease and Baylor Research Institute, Baylor University Medical Center Dallas, TX, USA.
Hunter Medical Research Institute · AUBaylor University Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Common functional polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, a key enzyme in folate and homocysteine metabolism, influence risk for a variety of complex disorders, including developmental, vascular, and neurological diseases. MTHFR deficiency is associated with elevation of homocysteine levels and alterations in the methylation cycle. Here, using young and aged Mthfr knockout mouse models, we show that mild MTHFR deficiency can lead to brain-region specific impairment of the methylation of Ser/Thr protein phosphatase 2A (PP2A). Relative to wild-type controls, decreased expression levels of PP2A and leucine carboxyl methyltransferase (LCMT1) were primarily observed in the hippocampus and cerebellum, and to a lesser extent in the cortex of young null Mthfr (-/-) and aged heterozygous Mthfr (+/-) mice. A marked down regulation of LCMT1 correlated with the loss of PP2A/Bα holoenzymes. Dietary folate deficiency significantly decreased LCMT1, methylated PP2A and PP2A/Bα levels in all brain regions examined from aged Mthfr (+/+) mice, and further exacerbated the regional effects of MTHFR deficiency in aged Mthfr (+/-) mice. In turn, the down regulation of PP2A/Bα was associated with enhanced phosphorylation of Tau, a neuropathological hallmark of Alzheimer's disease (AD). Our findings identify hypomethylation of PP2A enzymes, which are major CNS phosphatases, as a novel mechanism by which MTHFR deficiency and Mthfr gene-diet interactions could lead to disruption of neuronal homeostasis, and increase the risk for a variety of neuropsychiatric disorders, including age-related diseases like sporadic AD.

Indexed as

Alzheimer’s diseasefolateLCMT1methylationMTHFRPP2ATau phosphorylation

Identifiers

PMID25202269
PMCPMC4141544
OpenAlexW2067153292

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.