Evidence map›Paper›PMID 31143191›Full record

ReviewFrontiers in immunology2019

ccf-mtDNA as a Potential Link Between the Brain and Immune System in Neuro-Immunological Disorders.

Stefano Gambardella, Fiona Limanaqi, Rosangela Ferese, Francesca Biagioni, Rosa Campopiano, Diego Centonze, Francesco Fornai

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

Review in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% 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

94 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.

  1. Pooled it
  2. Article
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  5. Review
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  8. Review
  9. Article
  10. Cell-Free DNA and Mitochondria in Parkinson's Disease.International journal of molecular sciences · 2025
    Review
  11. The Immunogenic Role of Self-DNA in T Cell Immunity.Clinical reviews in allergy & immunology · 2025
    Review
  12. Article
  13. Review
  14. Article
  15. A pain from the nose to the head: neurological commitment during long COVID.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review

34 more citing papers are in PubMed but not listed here.

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 1 country.

Stefano GambardellaI.R.C.C.S Neuromed, Via Atinense, Pozzilli, Italy.
Fiona LimanaqiHuman Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Rosangela FereseI.R.C.C.S Neuromed, Via Atinense, Pozzilli, Italy.
Francesca BiagioniI.R.C.C.S Neuromed, Via Atinense, Pozzilli, Italy.
Rosa CampopianoI.R.C.C.S Neuromed, Via Atinense, Pozzilli, Italy.
Diego CentonzeI.R.C.C.S Neuromed, Via Atinense, Pozzilli, Italy.
Francesco FornaiI.R.C.C.S Neuromed, Via Atinense, Pozzilli, Italy.
Istituto Neurologico Mediterraneo · ITUniversity of Pisa · ITUniversity of Rome Tor Vergata · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fragments of mitochondrial DNA (mtDNA) are released outside the cell and they appear to persist in extracellular fluids as circulating, cell-free, mtDNA (ccf-mtDNA). When compared to nuclear DNA, such a double stranded mtDNA is more resistant to nuclease degradation. In fact, it is stable extracellularly where it can be detected in both plasma and cerebrospinal fluid (CSF), here acting as a potential biomarker in various disorders. In neurological diseases (Alzheimer's disease, Parkinson's disease and end-stage progressive Multiple Sclerosis), a decreased amount of CSF ccf-mtDNA is related with progressive cell dysfunction. This suggests an alteration in neuronal mtDNA levels (mtDNA replication, degradation and depletion) in vulnerable brain regions at early stages of neurodegeneration leading to reduced mtDNA release, which takes place before actual cell death occurs. On the other hand, elevated CSF ccf-mtDNA levels are reported in acute phases of relapsing-remitting Multiple Sclerosis (RRMS). This occurs during acute inflammation, which anticipates the neurodegenerative process. Thus, an increase in inflammatory cells in the affected regions is expected to add on mtDNA release into the CSF. In addition, similarly to bacterial DNA, the non-methylated CpG sites of mtDNA, which activate innate immunity and inflammation, are likely to participate in the molecular mechanisms of disease. Thus, ccf-mtDNA may represent a powerful biomarker for disease screening and prognosis at early stage, although its biological role may extend to generating the neurobiology of disease. The present manuscript discusses recent experimental findings in relationship with clinical evidence comparing neuro-immunological features of neurodegenerative disorders with frankly neuro-infectious diseases.

Indexed as

Cell-Free Nucleic AcidsDisease SusceptibilityDNA, MitochondrialImmune SystemNeuroimmunomodulationAnimalsBiomarkersBrainExosomesGene Expression RegulationHumansMicroRNAsMitochondriaNervous System DiseasesNeurodegenerative DiseasesSignal TransductionBiomarkersCell-Free Nucleic AcidsDNA, MitochondrialMicroRNAscirculating cell-free mtDNAexosomesmitochondriamtDNAneuro-immunity

Identifiers

PMID31143191
PMCPMC6520662
OpenAlexW2944647162

What OpenQuestion holds

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LicenceCC BY
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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.