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 axons. Increasing evidence points to an epigenetic component in the regulation of repair SC gene expression 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.
Highlights
Epigenetic markers such as acetylation or methylation can change gene expression.Acetylation depends on the opposite action of Histone acetyl transferases (HATs) and Histone deacetylases (HDACs), which acetylate and deacetylate histones, respectively.HDACs have been shown to play a critical role in peripheral nerve myelination and remyelination following injury
This review focuses on the role of HDACs in Schwann cells (SC) biology in both development and repair, as well as on genetic compensation between HDACs, a genetic mechanism that is gaining relevance as suggested by recent studies
Gerber et al further describe in their single cell sequencing data that SCs are not the main cell source for Hdac4, Hdac6, Hdac7, and Hdac11 gene expression levels during development, with fibroblast-related cells and endothelial cells contributing
Summary
Epigenetic markers such as acetylation or methylation can change gene expression. Acetylation depends on the opposite action of Histone acetyl transferases (HATs) and Histone deacetylases (HDACs), which acetylate and deacetylate histones, respectively. After an injury in the PNS, Schwann cells (SCs) can differentiate into a repair phenotype. This change in the phenotype is controlled by JUN, a transcription factor that is upregulated after injury. There is redundancy in HDAC expression, suggesting that there is genetic compensation of HDACs in the PNS: when one HDAC is depleted, another is upregulated, and peripheral nerve myelination and maintenance is conserved [6]. HDACs most frequently repress gene transcription by forming a complex with transcription factors and other proteins to regulate fundamental cellular processes such as cell cycle progression, survival, and differentiation [10]. We will further describe only HDAC classes I, II, and IV, and discuss the growing evidence for their roles in SC biology and nerve regeneration. HODftAenC,1HanDdAHCD1 AanCd2 HarDe AreCcr2uaitreedretocrgueittheedr,tofogremthienrg, ftohremsianmgethcoe-sraempreescsoo-recpormespsloerx,cosumcphleaxs, tshuechnuacslethoseonmuecrleemosoodmeleinrgemanodedlienagcaetnydladseacoetmylpalseexc(oNmupRleDx),(NSiunR3Dc)o,mSipnl3exc,omCopRleExS, TCocRomESpTlecxo,mopr ltehxe, omrithoteicmdietoatciectydleaasceectyomlaspelecxom(MpilDexA(CM).iHDADCA)C. 3H’sDeAnCzy3m’saetniczaycmtiavtiitcyaisctsiwviittychisedswointcwhehdenonit winhteernacitsiwntietrhatchtse wdeiathcetthyeladseeacetitvyalatisoenadcotimvaatiinon(DdAoDm)aoinf N(DCAODR)1oafndNCSMORT1 (aanlsdoScMallReTd (NalCsoOcRa2l)l,edfoNrmCiOngRt2h),efNorCmOinRg/tShMe RNTCcOoRm/pSlMexR[T7,c1o6m,18p]l.ex [7,16,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
