8f4da04afb794109726ca4db54cde692 ijms-26-06277.pdf 7fe142d5957012e0171541a927e91f99f6b7c861 ijms-26-06277.pdf 45017867643d1fa76f40af36aca27a5fcd9e26ef8e1ddb7011a8c62acd88dc37 ijms-26-06277.pdf Title: Histone Acetylation in Central and Peripheral Nervous System Injuries and Regeneration: Epigenetic Dynamics and Therapeutic Perspectives Subject: Traumatic injuries to the peripheral (PNS) and central nervous systems (CNS) trigger distinct regenerative responses, with the PNS displaying limited regenerative capacity and the CNS remaining largely refractory. Recent research highlights the role of epigenetic modifications, particularly histone acetylation, in modulating the gene expression programs that drive axonal regeneration. This review synthesizes current findings on post-translational histone modifications, focusing on histone acetyltransferases (HATs), histone deacetylases (HDACs), and epigenetic readers, in addition to their impact on neuronal and non-neuronal cells following injury. While HATs like p300/CBP and PCAF promote the expression of regeneration-associated genes, HDAC inhibition has been shown to facilitate neurite outgrowth, neuroprotection, and functional recovery in both PNS and CNS models. However, HDAC3, HDAC5, and HDAC6 demonstrate context- and cell-type-specific roles in both promoting and limiting regenerative processes. The review also highlights cell-specific findings that have been scarcely covered in the previous literature. Thus, the immunomodulatory roles of epigenetic regulators in microglia and macrophages, their involvement in remyelination via Schwann cells and oligodendrocytes, and their impact on astrocyte function are within the scope of this review. Closely considering cell-context specificity is critical, as some targets can exert opposite effects depending on the cell type involved. This represents a major challenge for current pharmacological therapies, which often lack precision. This complexity underscores the need to develop strategies that allow for cell-specific delivery or target regulators with converging beneficial effects across cell types. Such approaches may enhance regenerative outcomes after CNS or PNS injury. Keywords: epigenetics; regeneration; histone acetylation Author: Georgina Palomés-Borrajo, Xavier Navarro and Clara Penas Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Sun Jun 29 05:59:50 2025 CEST ModDate: Sun Jun 29 07:11:13 2025 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 24 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1919307 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- QKZKVH+VnURWPalladioL Type 1 Custom yes yes yes 10 0 FNXAPU+URWPalladioL-Roma Type 1 Custom yes yes yes 16 0 WTLBBU+URWPalladioL-Bold Type 1 Custom yes yes yes 22 0 OLEXJH+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 DXWSGT+CMSY10 Type 1 Builtin yes yes yes 56 0 DUJUUF+PazoMath-Italic Type 1 Builtin yes yes yes 64 0 KMPOKB+PalatinoLinotype TrueType WinAnsi yes yes no 79 0 JDWIZJ+EURM10 Type 1 Builtin yes yes yes 92 0 KMPOKB+PalatinoLinotype TrueType WinAnsi yes yes no 105 0 KMPOKB+PalatinoLinotype TrueType WinAnsi yes yes no 136 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-09-09 03:10:33 CEST RepresentationInformation: ijms-26-06277.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-09-08 10:41:22 CEST Size: 1919307 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 561 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Post-Translational Histone Modifications Destination: section.2 Children: Item: Title: Histone Acetylation Destination: subsection.2.1 Item: Title: Histone Methylation Destination: subsection.2.2 Item: Title: Histone Acetylation and Its Influence on Axonal Regeneration Destination: section.3 Children: Item: Title: Histone Acetyltransferases (HATs) Destination: subsection.3.1 Children: Item: Title: p300/CBP Destination: subsubsection.3.1.1 Item: Title: PCAF Destination: subsubsection.3.1.2 Item: Title: Histone Deacetylases (HDACs) Destination: subsection.3.2 Children: Item: Title: Class I HDACs Destination: subsubsection.3.2.1 Item: Title: Class II HDACs Destination: subsubsection.3.2.2 Item: Title: Class III HDACs Destination: subsubsection.3.2.3 Item: Title: Readers of Acetylated Residues Destination: subsection.3.3 Children: Item: Title: BET Proteins Destination: subsubsection.3.3.1 Item: Title: BRG1 Destination: subsubsection.3.3.2 Item: Title: Epigenetic Modifications in Non-Neuronal Cells and Consequences for Neural Regeneration Destination: section.4 Children: Item: Title: Myeloid Cells: Microglia and Macrophages Destination: subsection.4.1 Item: Title: Myelinating Cells: Schwann Cells and Oligodendrocytes Destination: subsection.4.2 Item: Title: Astrocytes Destination: subsection.4.3 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: Histone Acetylation in Central and Peripheral Nervous System Injuries and Regeneration: Epigenetic Dynamics and Therapeutic Perspectives Author: Georgina Palomés-Borrajo, Xavier Navarro and Clara Penas Subject: Traumatic injuries to the peripheral (PNS) and central nervous systems (CNS) trigger distinct regenerative responses, with the PNS displaying limited regenerative capacity and the CNS remaining largely refractory. Recent research highlights the role of epigenetic modifications, particularly histone acetylation, in modulating the gene expression programs that drive axonal regeneration. This review synthesizes current findings on post-translational histone modifications, focusing on histone acetyltransferases (HATs), histone deacetylases (HDACs), and epigenetic readers, in addition to their impact on neuronal and non-neuronal cells following injury. While HATs like p300/CBP and PCAF promote the expression of regeneration-associated genes, HDAC inhibition has been shown to facilitate neurite outgrowth, neuroprotection, and functional recovery in both PNS and CNS models. However, HDAC3, HDAC5, and HDAC6 demonstrate context- and cell-type-specific roles in both promoting and limiting regenerative processes. The review also highlights cell-specific findings that have been scarcely covered in the previous literature. Thus, the immunomodulatory roles of epigenetic regulators in microglia and macrophages, their involvement in remyelination via Schwann cells and oligodendrocytes, and their impact on astrocyte function are within the scope of this review. Closely considering cell-context specificity is critical, as some targets can exert opposite effects depending on the cell type involved. This represents a major challenge for current pharmacological therapies, which often lack precision. This complexity underscores the need to develop strategies that allow for cell-specific delivery or target regulators with converging beneficial effects across cell types. Such approaches may enhance regenerative outcomes after CNS or PNS injury. 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652 Annotation: Subtype: Link Rect: 190, 616, 228, 627 Annotation: Subtype: Link Rect: 219, 590, 257, 601 Annotation: Subtype: Link Rect: 496, 565, 534, 576 Annotation: Subtype: Link Rect: 327, 526, 365, 537 Annotation: Subtype: Link Rect: 494, 501, 531, 512 Annotation: Subtype: Link Rect: 230, 462, 267, 473 Annotation: Subtype: Link Rect: 519, 437, 557, 448 Annotation: Subtype: Link Rect: 59, 425, 95, 435 Annotation: Subtype: Link Rect: 293, 399, 330, 410 Annotation: Subtype: Link Rect: 336, 399, 372, 410 Annotation: Subtype: Link Rect: 265, 373, 303, 384 Annotation: Subtype: Link Rect: 309, 373, 345, 384 Annotation: Subtype: Link Rect: 265, 348, 303, 358 Annotation: Subtype: Link Rect: 59, 310, 96, 320 Annotation: Subtype: Link Rect: 180, 284, 218, 295 Annotation: Subtype: Link Rect: 212, 258, 250, 269 Annotation: Subtype: Link Rect: 301, 233, 338, 244 Annotation: Subtype: Link Rect: 331, 194, 368, 205 Annotation: Subtype: Link Rect: 213, 169, 250, 180 Annotation: Subtype: Link Rect: 183, 144, 220, 154 Annotation: Subtype: Link Rect: 226, 144, 262, 154 Annotation: Subtype: Link Rect: 226, 118, 263, 129 Annotation: Subtype: Link Rect: 270, 118, 306, 129 Checksum: 067410b6 Type: CRC32 Checksum: 8f4da04afb794109726ca4db54cde692 Type: MD5 Checksum: 7fe142d5957012e0171541a927e91f99f6b7c861 Type: SHA-1 Checksum: 45017867643d1fa76f40af36aca27a5fcd9e26ef8e1ddb7011a8c62acd88dc37 Type: SHA-256