Evidence map›Paper›PMID 25342943›Full record

ArticleCurrent neuropharmacology2014

Calcium-Sensing Receptors of Human Astrocyte-Neuron Teams: Amyloid-β-Driven Mediators and Therapeutic Targets of Alzheimer's Disease.

I Dal Prà, A Chiarini, R Pacchiana, E Gardenal, B Chakravarthy, J F Whitfield, U Armato

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

Article in Current neuropharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

23 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Review
  3. OATP1A2 mediates AβFrontiers in pharmacology · 2024
    Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade.Journal of Alzheimer's disease : JAD · 2018
    Review
  16. Astrocyte and Alzheimer's disease.Journal of neurology · 2017
    Review
  17. Article
  18. Review
  19. Article
  20. Article
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 3 institutions in 3 countries.

I Dal PràHistology & Embryology Section, Department of Life & Reproduction Sciences, University of Verona Medical School, Verona, Venetia, Italy.
A ChiariniHistology & Embryology Section, Department of Life & Reproduction Sciences, University of Verona Medical School, Verona, Venetia, Italy.
R PacchianaHistology & Embryology Section, Department of Life & Reproduction Sciences, University of Verona Medical School, Verona, Venetia, Italy.
E GardenalHistology & Embryology Section, Department of Life & Reproduction Sciences, University of Verona Medical School, Verona, Venetia, Italy.
B ChakravarthyNational Research Council of Canada, Ottawa, Ontario, Canada.
J F WhitfieldNational Research Council of Canada, Ottawa, Ontario, Canada.
U ArmatoHistology & Embryology Section, Department of Life & Reproduction Sciences, University of Verona Medical School, Verona, Venetia, Italy.
University of Verona · ITNational Academies of Sciences, Engineering, and Medicine · USNational Research Council Canada · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

It is generally assumed that the neuropathology of sporadic (late-onset or nonfamilial) Alzheimer's disease (AD) is driven by the overproduction and spreading of first Amyloid-βx-42 (Aβ42) and later hyperphosphorylated (hp)-Tau oligomeric "infectious seeds". Hitherto, only neurons were held to make and spread both oligomer types; astrocytes would just remove debris. However, we have recently shown that exogenous fibrillar or soluble Aβ peptides specifically bind and activate the Ca(2+)-sensing receptors (CaSRs) of untransformed human cortical adult astrocytes and postnatal neurons cultured in vitro driving them to produce, accrue, and secrete surplus endogenous Aβ42. While the Aβ-exposed neurons start dying, astrocytes survive and keep oversecreting Aβ42, nitric oxide (NO), and vascular endothelial growth factor (VEGF)-A. Thus astrocytes help neurons' demise. Moreover, we have found that a highly selective allosteric CaSR agonist ("calcimimetic"), NPS R-568, mimics the just mentioned neurotoxic actions triggered by Aβ●CaSR signaling. Contrariwise, and most important, NPS 2143, a highly selective allosteric CaSR antagonist ("calcilytic"), fully suppresses all the Aβ●CaSR signaling-driven noxious actions. Altogether our findings suggest that the progression of AD neuropathology is promoted by unceasingly repeating cycles of accruing exogenous Aβ42 oligomers interacting with the CaSRs of swelling numbers of astrocyte-neuron teams thereby recruiting them to overrelease additional Aβ42 oligomers, VEGF-A, and NO. Calcilytics would beneficially break such Aβ/CaSR-driven vicious cycles and hence halt or at least slow the otherwise unstoppable spreading of AD neuropathology.

Indexed as

Alzheimer’s diseaseamyloid-beta oligomersastrocyte-neuron teamscalcilyticscalcimimetics.calcium-sensing receptor

Identifiers

PMID25342943
PMCPMC4207075
OpenAlexW2121830956

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.