Histone Acetylation in Central and Peripheral Nervous System Injuries and Regeneration : Epigenetic Dynamics and Therapeutic Perspectives
Palomés Borrajo, Georgina (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Navarro, X. (Xavier) (Universitat Autònoma de Barcelona. Institut de Neurociències)
Penas Pérez, Clara (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Data:	2025
Resum:	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.
Ajuts:	Agencia Estatal de Investigación PID2022-140655OB-I00 Agencia Estatal de Investigación CPP2022-009550
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article de revisió ; recerca ; Versió publicada
Matèria:	Epigenetics ; Regeneration ; Histone acetylation
Publicat a:	International journal of molecular sciences, Vol. 26. Issue 13 (June 2025) , art. 6277, ISSN 1422-0067

DOI: 10.3390/ijms26136277
PMID: 40650056

24 p, 1.8 MB

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