ArticleThe Journal of biological chemistry2016
Selective Inhibition of the Mitochondrial Permeability Transition Pore Protects against Neurodegeneration in Experimental Multiple Sclerosis.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Smoking induces DNA methylation changes in Multiple Sclerosis patients with exposure-response relationship.Scientific reports · 2017Pooled it
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Mitochondria-Targeting Moieties Based on N-Tethered Pyridinium Cations.Angewandte Chemie (International ed. in English) · 2026Article
- APOE4 exacerbates glucocorticoid stress hormone-induced tau pathology via mitochondrial dysfunction.Cell death & disease · 2026Article
- Human Cyclophilins-An Emerging Class of Drug Targets.Medicinal research reviews · 2026Review
- Lipophilic Cations as Mitochondria-Targeting Moieties: Recent Progress and Design Principles for Medicinal Chemistry.Journal of medicinal chemistry · 2025Review
- Biofilm-dispersal patterns in ESKAPE pathogens.Archives of microbiology · 2025Review
- Macrocycle-based PROTACs selectively degrade cyclophilin A and inhibit HIV-1 and HCV.Nature communications · 2025Article
- Neuroprotection against beta-amyloid toxicity by the novel estrogen receptor modulator STX requires convergent signaling pathways.Frontiers in molecular neuroscience · 2025Article
- Cladribine tablets in the new multiple sclerosis era.Therapeutic advances in neurological disorders · 2025Review
- Pathogenic synergy: dysfunctional mitochondria and neuroinflammation in neurodegenerative diseases associated with aging.Frontiers in aging · 2025Review
- Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.Molecular cancer · 2024Review
- Should We Consider Neurodegeneration by Itself or in a Triangulation with Neuroinflammation and Demyelination? The Example of Multiple Sclerosis and Beyond.International journal of molecular sciences · 2024Review
- Evaluating the potential of non-immunosuppressive cyclosporin analogs for targeting Toxoplasma gondii cyclophilin: Insights from structural studies.Protein science : a publication of the Protein Society · 2024Article
- Remyelinating Drugs at a Crossroad: How to Improve Clinical Efficacy and Drug Screenings.Cells · 2024Review
- Delocalized quinolinium-macrocyclic peptides, an atypical chemotype for CNS penetration.Science advances · 2024Article
- The neuropathobiology of multiple sclerosis.Nature reviews. Neuroscience · 2024Review
- Review
- Mitochondrial Dysfunction Causes Cell Death in Patients Affected by Fragile-X-Associated Disorders.International journal of molecular sciences · 2024Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
The mitochondrial permeability transition pore is a recognized drug target for neurodegenerative conditions such as multiple sclerosis and for ischemia-reperfusion injury in the brain and heart. The peptidylprolyl isomerase, cyclophilin D (CypD, PPIF), is a positive regulator of the pore, and genetic down-regulation or knock-out improves outcomes in disease models. Current inhibitors of peptidylprolyl isomerases show no selectivity between the tightly conserved cyclophilin paralogs and exhibit significant off-target effects, immunosuppression, and toxicity. We therefore designed and synthesized a new mitochondrially targeted CypD inhibitor, JW47, using a quinolinium cation tethered to cyclosporine. X-ray analysis was used to validate the design concept, and biological evaluation revealed selective cellular inhibition of CypD and the permeability transition pore with reduced cellular toxicity compared with cyclosporine. In an experimental autoimmune encephalomyelitis disease model of neurodegeneration in multiple sclerosis, JW47 demonstrated significant protection of axons and improved motor assessments with minimal immunosuppression. These findings suggest that selective CypD inhibition may represent a viable therapeutic strategy for MS and identify quinolinium as a mitochondrial targeting group for in vivo use.
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What OpenQuestion holds
Registered trials
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.