ArticleThe Journal of clinical investigation2016
Blocking mitochondrial calcium release in Schwann cells prevents demyelinating neuropathies.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 2 papers.
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
2 citing papers in PubMed, 14 citations in OpenAlex.
- Peripheral Glial Cells in the Development of Diabetic Neuropathy.Frontiers in neurology · 2018Review
- Axon degeneration: make the Schwann cell great again.Neural regeneration research · 2017Review
Corrections and comments
- Retraction · 2017-03-01Concerns/Issues about Data · Concerns/Issues about Image · Error in Image · Investigation by Company/Institution · Investigation by Journal/Publisher · Investigation by Third Party · Upgrade/Update of Prior Notice(s) · · See also: https://pubpeer.com/publications/17DFDDA4F57F2F519D92184E424B51#fb48306
- Correction · 2016-03-07Error in Image · Updated to Retraction · · See also: https://pubpeer.com/publications/17DFDDA4F57F2F519D92184E424B51#fb48306
- Expression of concern · 2016-07-01Concerns/Issues about Image · Error in Image · Investigation by Journal/Publisher · Updated to Retraction · Upgrade/Update of Prior Notice(s) · · See also: https://pubpeer.com/publications/17DFDDA4F57F2F519D92184E424B51#fb48306
- Erratum issued
- Expression of concern
- Retracted
Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Schwann cells produce myelin sheath around peripheral nerve axons. Myelination is critical for rapid propagation of action potentials, as illustrated by the large number of acquired and hereditary peripheral neuropathies, such as diabetic neuropathy or Charcot-Marie-Tooth diseases, that are commonly associated with a process of demyelination. However, the early molecular events that trigger the demyelination program in these diseases remain unknown. Here, we used virally delivered fluorescent probes and in vivo time-lapse imaging in a mouse model of demyelination to investigate the underlying mechanisms of the demyelination process. We demonstrated that mitochondrial calcium released by voltage-dependent anion channel 1 (VDAC1) after sciatic nerve injury triggers Schwann cell demyelination via ERK1/2, p38, JNK, and c-JUN activation. In diabetic mice, VDAC1 activity was altered, resulting in a mitochondrial calcium leak in Schwann cell cytoplasm, thereby priming the cell for demyelination. Moreover, reduction of mitochondrial calcium release, either by shRNA-mediated VDAC1 silencing or pharmacological inhibition, prevented demyelination, leading to nerve conduction and neuromuscular performance recovery in rodent models of diabetic neuropathy and Charcot-Marie-Tooth diseases. Therefore, this study identifies mitochondria as the early key factor in the molecular mechanism of peripheral demyelination and opens a potential opportunity for the treatment of demyelinating peripheral neuropathies.
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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.