Evidence map›Paper›PMID 33329338›Full record

SynthesisFrontiers in neurology2020

RANK/RANKL/OPG Signaling in the Brain: A Systematic Review of the Literature.

Anton Glasnović, Niall O'Mara, Nataša Kovačić, Danka Grčević, Srećko Gajović

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

Synthesis in Frontiers in neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.

  1. Pooled it
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  6. Multi-dimensional plasma proteomic profiling elucidates molecular mechanisms and pathophysiological networks in pediatric severe traumatic brain injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
  7. Aging-Driven Inter-Organ Crosstalk in Postmenopausal Osteoporosis: From Immunometabolic Drift to Multisystem Frailty.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Review
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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

5 authors at 2 institutions in 2 countries.

Anton GlasnovićDepartment of Histology and Embryology, Zagreb University School of Medicine, Zagreb, Croatia.
Niall O'MaraDepartment of Medicine, Cork University Hospital, Cork, Ireland.
Nataša KovačićCroatian Institute for Brain Research, Zagreb University School of Medicine, Zagreb, Croatia.
Danka GrčevićCroatian Institute for Brain Research, Zagreb University School of Medicine, Zagreb, Croatia.
Srećko GajovićDepartment of Histology and Embryology, Zagreb University School of Medicine, Zagreb, Croatia.
University of Zagreb · HRCork University Hospital · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Together with its dominant immunological and bone remodeling involvement, RRO axis, comprising of receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) signaling, is as well-implicated in CNS functioning and corresponding pathologies. The CNS aspects of RANKL/RANK/OPG (RRO) axis were systematically reviewed. With search 10 databases, and 7 additional resources from first article publication to July 2019, resulted in total 2,222 hits, from which 33 relevant articles were selected. The elements of RRO axis in CNS include cells involved in neuroinflammation, predominantly in microglia, but as well in resident macrophages and inflammatory cells migrating across the blood-brain barrier. The expression in neurons and oligodendrocytes is mainly confined to processes of differentiation and cell death. RRO axis tunes the neuroinflammatory response, depending on the molecular, cellular and pathological context. RANK/RANKL signaling is neuroprotective in TLR-mediated inflammation, while OPG seems detrimental in stroke, but beneficial in multiple sclerosis. The levels of RRO axis elements can serve as biomarkers in the blood and cerebrospinal fluid. They act as neuroprotectant after brain damage even being implicated in body weight- and thermo-regulation. As derivatives of RRO axis already exist as therapeutic agents in bone remodeling, it would be intriquing to see if these or new RRO-based pharmaceuticals would appear effective in CNS therapies.

Indexed as

BBB rupturingmultiple sclerosis - etiologyneural mediatorsneuroinflammatory cytokinesOPG - RANKL - RANKstroke repair

Identifiers

PMID33329338
PMCPMC7710989
OpenAlexW3103655969

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.