Adaptive autophagy reprogramming in Schwann cells during peripheral demyelination

Jo, Young Rae; Oh, Yuna; Kim, Young Hee; Shin, Yoon Kyung; Kim, Hye Ran; Go, Hana; Shin, Jaekyoon; Park, Hye Ji; Koh, Hyongjong; Kim, Jong Kuk; Shin, Jung Eun; Lee, Jun Young; Park, Hwan Tae

doi:10.1007/s00018-022-04683-7

Cited by 10 publications

(6 citation statements)

References 42 publications

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“…It has been shown that demyelinating SCs during Wallerian demyelination after axonal injury utilize autophagy for myelin clearance 22 – 24 . We recently reported that demyelinating SCs in Wallerian demyelination employ autophagy machineries for excreting degenerating myelin and that p62 secretion from SCs could be an index of such demyelination activity of SCs 25 , 26 . Those reports further support our hypothesis of the potential SC source of plasma p62 elevation in patients with demyelinating CMT.…”

Section: Discussionmentioning

confidence: 99%

p62/sequestosome-1 as a severity-reflecting plasma biomarker in Charcot–Marie–Tooth disease type 1A

Yoon,

Kim,

Nam

et al. 2024

Sci Rep

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Autophagy is a self-degradation system for recycling to maintain homeostasis. p62/sequestosome-1 (p62) is an autophagy receptor that accumulates in neuroglia in neurodegenerative diseases. The objective of this study was to determine the elevation of plasma p62 protein levels in patients with Charcot–Marie–Tooth disease 1A (CMT1A) for its clinical usefulness to assess disease severity. We collected blood samples from 69 CMT1A patients and 59 healthy controls. Plasma concentrations of p62 were analyzed by ELISA, and we compared them with Charcot-Marie-Tooth neuropathy score version 2 (CMTNSv2). A mouse CMT1A model (C22) was employed to determine the source and mechanism of plasma p62 elevation. Plasma p62 was detected in healthy controls with median value of 1978 pg/ml, and the levels were significantly higher in CMT1A (2465 pg/ml, p < 0.001). The elevated plasma p62 levels were correlated with CMTNSv2 (r = 0.621, p < 0.0001), motor nerve conduction velocity (r = − 0.490, p < 0.0001) and disease duration (r = 0.364, p < 0.01). In C22 model, increased p62 expression was observed not only in pathologic Schwann cells but also in plasma. Our findings indicate that plasma p62 measurement could be a valuable tool for evaluating CMT1A severity and Schwann cell pathology.

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Section: Discussionmentioning

confidence: 99%

p62/sequestosome-1 as a severity-reflecting plasma biomarker in Charcot–Marie–Tooth disease type 1A

Yoon,

Kim,

Nam

et al. 2024

Sci Rep

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“…ATG1, ATG13, and ATG17 expression products so combine to create the autophagy initiation complex (ULK1 complex) (Gao et al 2019). The demyelinating Schwann cells seemed to utilize myelin membranes for secretory phagophore formation and employed p62/sequestosome-1 (p62) as an autophagy receptor for myelin excretion (Jo et al 2023). LC3 precursors form after protease process LC3-I.…”

Section: Discussionmentioning

confidence: 99%

Identifying Autophagy-Related Genes contributing to Diabetes Peripheral Neuropathy

Xing

Liu

et al. 2023

Preprint

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Purpose Diabetes has a common complication called diabetic peripheral neuropathy (DPN), whose exact pathophysiology is still unknown. In ischemic reperfusion injury to nerve tissues, the treatment of neurodegenerative illnesses, and the repair of nerve tissue injuries, autophagy is crucial. Through bioinformatics analysis and validation, we hope to pinpoint the possible autophagy-related differential expressed genes (DEGs) of DPN. Methods The GEO database provided the mRNA expression profile dataset GSE185011. R software was used to look for possible DPN autophagy-related DEGs. Then, for the autophagy-related DEGs, protein-protein interactions (PPI), correlation analysis, gene-ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out. In the validation set GSE95849, the RNA expression of autophagy-related DEGs was verified in blood samples from DPN patients and healthy controls. Results Between 5 DPN patients and 5 healthy controls, a total of 33 autophagy-related DEGs (5 up-regulated genes and 28 down-regulated genes) were found. The PPI analysis showed interactions between these autophagy-related DEGs. The GO and KEGG enrichment analyses revealed a number of enriched terms including mitophagy and autophagy. The results of the validation set demonstrated that the expression levels of the genes P4HB, GAPDH, CTSB and RAB7A were significantly decreased, ATG5, CASP3, SQSTM1, ULK1, and 9 other genes in DPN patients were significantly up-regulated in the DPN patients, which were compatible with the bioinformatics analysis of mRNA microarray. Conclusion Through bioinformatics research, we identified 17 putative autophagy-related DEGs in DPN. By regulating autophagy, ATG5, CASP3, SQSTM1, ULK1, and another 13 genes may have an impact on DPN formation. These findings might deepen our understanding of DPN and help with DPN treatment.

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“…Generally, Wallerian degeneration of the distal nerve stumps occurs immediately after peripheral nerve injury 40,41 . In Wallerian degeneration, the damaged myelin sheath and axon fragments are removed, and a microenvironment suitable for the regrowth of axons is formed in the wound area, which is a key process of peripheral nerve regeneration 25,42,43 .…”

Section: Discussionmentioning

confidence: 99%

“…Wallerian degeneration is a series of complex changes in the distal nerve tissue after peripheral nerve injury, which is the basis and prerequisite for the regeneration of injured peripheral nerve 25,26 . With the progress of Wallerian degeneration, the damaged nerve myelin gradually deformed and fragmented until it was nally swallowed by macrophages.…”

Section: Spinal Cord Injury Delays Wallerian Degeneration Of the Scia...mentioning

confidence: 99%

Analysis of miRNA expression profile of sciatic nerve in rats with spinal cord injury

Jiang

Zhang

et al. 2023

Preprint

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After spinal cord injury, the downstream peripheral nerves lose control, and the tissues lose the protection of peripheral nerves, which is easy to cause skin and soft tissue injury and wound difficult to heal. However, the underlying mechanisms are still unknown. In order to explore the mechanism of functional changes in peripheral nerves deprived of spinal cord control, we established a model of sciatic nerve transection injury combined with spinal cord transection injury in Sprague-Dawley (SD) rats, and small RNA sequencing analysis, tissue staining and molecular experiments were used to analyze the changes in miRNA expression and degeneration of peripheral nerve stump. The results showed that after loss of spinal cord innervation, the response of rats to sciatic nerve injury was weakened, and Wallerian degeneration could not occur normally and angiogenesis was abnormal. Moreover, differentially expressed miRNAs were detected in the sciatic nerve stump of the two groups of rats with or without spinal cord injury. Specifically, miR-134-5p and miR-142-5p were decreased in the sciatic nerve stump after spinal cord injury. Therefore, we suggest that spinal cord injury may inhibit the repair process of sciatic nerve injury by down-regulating the expression of miR-134-5p / miR-142-5p.

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Adaptive autophagy reprogramming in Schwann cells during peripheral demyelination

Cited by 10 publications

References 42 publications

p62/sequestosome-1 as a severity-reflecting plasma biomarker in Charcot–Marie–Tooth disease type 1A

p62/sequestosome-1 as a severity-reflecting plasma biomarker in Charcot–Marie–Tooth disease type 1A

Identifying Autophagy-Related Genes contributing to Diabetes Peripheral Neuropathy

Analysis of miRNA expression profile of sciatic nerve in rats with spinal cord injury

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