Emerging Role of HDACs in Regeneration and Ageing in the Peripheral Nervous System: Repair Schwann Cells as Pivotal Targets.
Por:
Gomez-Sanchez JA, Patel N, Martirena F, Fazal SV, Mutschler C and Cabedo H
Publicada:
10 mar 2022
Ahead of Print:
10 mar 2022
Resumen:
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 Zn(2+)-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.
Filiaciones:
:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas, 03550 San Juan de Alicante, Spain
Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), 03010 Alicante, Spain
:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas, 03550 San Juan de Alicante, Spain
Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), 03010 Alicante, Spain
Martirena F:
Department of Hematology, General University Hospital of Elda, 03600 Elda, Spain
Fazal SV:
John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK
Wellcome-MRC Cambridge Stem Cell Institute, Puddicombe Way, Cambridge CB2 0AW, UK
Mutschler C:
John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK
:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas, 03550 San Juan de Alicante, Spain
Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), 03010 Alicante, Spain
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