Evidence map›Paper›PMID 35018577›Full record

ArticleMolecular neurobiology2022

Translocator Protein Ligand PIGA1138 Reduces Disease Symptoms and Severity in Experimental Autoimmune Encephalomyelitis Model of Primary Progressive Multiple Sclerosis.

Chiara Tremolanti, Chiara Cavallini, Laurence Meyer, Christian Klein, Eleonora Da Pozzo, Barbara Costa, Lorenzo Germelli, Sabrina Taliani, Christine Patte-Mensah, Ayikoé-Guy Mensah-Nyagan

Abstract read
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In one paragraph

Article in Molecular neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

8 citing papers in PubMed, 13 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

10 authors at 3 institutions in 2 countries.

Chiara Tremolanti *Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Bâtiment CRBS de la Faculté de Médecine, 1 rue Eugène Boeckel, 67 000, Strasbourg, France.
Chiara Cavallini *Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Bâtiment CRBS de la Faculté de Médecine, 1 rue Eugène Boeckel, 67 000, Strasbourg, France.
Laurence MeyerBiopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Bâtiment CRBS de la Faculté de Médecine, 1 rue Eugène Boeckel, 67 000, Strasbourg, France.
Christian KleinBiopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Bâtiment CRBS de la Faculté de Médecine, 1 rue Eugène Boeckel, 67 000, Strasbourg, France.
Eleonora Da PozzoDepartment of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
Barbara CostaDepartment of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
Lorenzo GermelliDepartment of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
Sabrina TalianiDepartment of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
Christine Patte-MensahBiopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Bâtiment CRBS de la Faculté de Médecine, 1 rue Eugène Boeckel, 67 000, Strasbourg, France.
Ayikoé-Guy Mensah-NyaganBiopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Bâtiment CRBS de la Faculté de Médecine, 1 rue Eugène Boeckel, 67 000, Strasbourg, France. gmensah@unistra.fr.
Inserm · FRUniversity of Pisa · ITUniversité de Strasbourg · FR

Funding

INSERM 1119Italian Ministry of Education, Universities and Research (MIUR) 2017MT3993Université de Strasbourg UMR_S 1119
6 · The paper itself

Abstract

Multiple sclerosis (MS) is an autoimmune and demyelinating disease of the central nervous system (CNS) caused by CNS infiltration of peripheral immune cells, immune-mediated attack of the myelin sheath, neuroinflammation, and/or axonal/neuronal dysfunctions. Some drugs are available to cope with relapsing-remitting MS (RRMS) but there is no therapy for the primary progressive MS (PPMS). Because growing evidence supports a regulatory role of the translocator protein (TSPO) in neuroinflammatory, demyelinating, and neurodegenerative processes, we investigated the therapeutic potential of phenylindolyilglyoxylamydes (PIGAs) TSPO ligands in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) mice mimicking the human PPMS. MOG-EAE C57Bl/6-mice were treated by TSPO ligands PIGA839, PIGA1138, or the vehicle. Several methods were combined to evaluate PIGAs-TSPO ligand effects on MOG-EAE symptoms, CNS infiltration by immune cells, demyelination, and axonal damages. PIGA1138 (15 mg/kg) drastically reduced MOG-EAE mice clinical scores, ameliorated motor dysfunctions assessed with the Catwalk device, and counteracted MOG-EAE-induced demyelination by preserving Myelin basic protein (MBP) expression in the CNS. Furthermore, PIGA1138-treatment prevented EAE-evoked decreased neurofilament-200 expression in spinal and cerebellar axons. Moreover, PIGA1138 inhibited peripheral immune-CD45 + cell infiltration in the CNS, suggesting that it may control inflammatory mechanisms involved in PPMS. Concordantly, PIGA1138 enhanced anti-inflammatory interleukin-10 serum level in MOG-EAE mice. PIGA1138-treatment, which increased neurosteroid allopregnanolone production, ameliorated all pathological biomarkers, while PIGA839, unable to activate neurosteroidogenesis in vivo, exerted only moderate/partial effects in MOG-EAE mice. Altogether, our results suggest that PIGA1138-based treatment may represent an interesting possibility to be explored for the innovation of effective therapies against PPMS.

Indexed as

Encephalomyelitis, Autoimmune, ExperimentalMultiple SclerosisMultiple Sclerosis, Chronic ProgressiveAnimalsLigandsMiceMice, Inbred C57BLMyelin-Oligodendrocyte GlycoproteinLigandsMyelin-Oligodendrocyte GlycoproteinDemyelinationExperimental autoimmune encephalomyelitisMultiple sclerosisMyelin diseaseNeuroinflammationNeuroprotectionTSPO ligands

Identifiers

PMID35018577
OpenAlexW4205464703

What OpenQuestion holds

Textmetadata
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.