Emerging Role of HDACs in Regeneration and Ageing in the Peripheral Nervous System: Repair Schwann Cells as Pivotal Targets
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Authors
Gomez-Sanchez, Jose Antonio
Patel, Nikiben
Martirena, Fernanda
Fazal, Shaline V
Mutschler, Clara
Cabedo, Hugo
Publication Date
2022-03-10Journal Title
International Journal of Molecular Sciences
ISSN
1422-0067
Publisher
MDPI AG
Volume
23
Issue
6
Language
eng
Type
Article
This Version
VoR
Metadata
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Gomez-Sanchez, J. A., Patel, N., Martirena, F., Fazal, S. V., Mutschler, C., & Cabedo, H. (2022). Emerging Role of HDACs in Regeneration and Ageing in the Peripheral Nervous System: Repair Schwann Cells as Pivotal Targets. International Journal of Molecular Sciences, 23 (6) https://doi.org/10.3390/ijms23062996
Abstract
The peripheral nervous system (PNS) has a remarkable regenerative capacity in comparison to the central nervous system (CNS), a phenomenon that is impaired during ageing. The ability of PNS axons to regenerate after injury is due to Schwann cells (SC) being reprogrammed into a repair phenotype called Repair Schwann cells. These repair SCs are crucial for supporting axonal growth after injury, myelin degradation in a process known as myelinophagy, neurotropic factor secretion, and axonal growth guidance through the formation of Büngner bands. After regeneration, repair SCs can remyelinate newly regenerated axons and support nonmyelinated ax-ons. Increasing evidence points to an epigenetic component in the regulation of repair SC gene ex-pression changes, which is necessary for SC reprogramming and regeneration. One of these epigenetic regulations is histone acetylation by histone acetyl transferases (HATs) or histone deacetylation by histone deacetylases (HDACs). In this review, we have focused particularly on three HDAC classes (I, II, and IV) that are Zn2+-dependent deacetylases. These HDACs are important in repair SC biology and remyelination after PNS injury. Another key aspect explored in this review is HDAC genetic compensation in SCs and novel HDAC inhibitors that are being studied to improve nerve regeneration.
Keywords
Nerve regeneration, Ageing, Schwann cell, Nerve injury, Myelin, Remyelination, Hdacs, Repair Schwann Cell, Hdacs Therapies, Schwann Cells, Axons, Peripheral Nervous System, Histone Deacetylases, Histones, Nerve Regeneration
Sponsorship
Ministerio de Economía y Competitividad (BFU2016-75864R and PID2019-109762RB-I00)
ISABIAL (UGP18-257 and UGP-2019-128)
Conselleria Educació Generalitat Valenciana (PROMETEO 2018/114)
Medical Research Council (UK) studentship (2251399)
Funder references
Medical Research Council (2251399)
Identifiers
35328416, PMC8951080
External DOI: https://doi.org/10.3390/ijms23062996
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336400
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