Display options
Cite
Spreafico M, Cafora M, Bragato C, et al. Targeting HDAC8 to ameliorate skeletal muscle differentiation in Duchenne muscular dystrophy. Pharmacol Res. 2021;170:105750doi: 10.1016/j.phrs.2021.105750.
Spreafico, M., Cafora, M., Bragato, C., Capitanio, D., Marasca, F., Bodega, B., De Palma, C., Mora, M., Gelfi, C., Marozzi, A., & Pistocchi, A. (2021). Targeting HDAC8 to ameliorate skeletal muscle differentiation in Duchenne muscular dystrophy. Pharmacological research, 170105750. https://doi.org/10.1016/j.phrs.2021.105750
Spreafico, Marco, et al. "Targeting HDAC8 to ameliorate skeletal muscle differentiation in Duchenne muscular dystrophy." Pharmacological research vol. 170 (2021): 105750. doi: https://doi.org/10.1016/j.phrs.2021.105750
Spreafico M, Cafora M, Bragato C, Capitanio D, Marasca F, Bodega B, De Palma C, Mora M, Gelfi C, Marozzi A, Pistocchi A. Targeting HDAC8 to ameliorate skeletal muscle differentiation in Duchenne muscular dystrophy. Pharmacol Res. 2021 Aug;170:105750. doi: 10.1016/j.phrs.2021.105750. Epub 2021 Jun 30. PMID: 34214631.
Copy Download .nbib Format: NLM
Share it on

Pharmacol Res. 2021 Aug;170:105750. doi: 10.1016/j.phrs.2021.105750. Epub 2021 Jun 30.

Targeting HDAC8 to ameliorate skeletal muscle differentiation in Duchenne muscular dystrophy.

Pharmacological research

Marco Spreafico, Marco Cafora, Cinzia Bragato, Daniele Capitanio, Federica Marasca, Beatrice Bodega, Clara De Palma, Marina Mora, Cecilia Gelfi, Anna Marozzi, Anna Pistocchi

Affiliations

  1. Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milan, Italy.
  2. Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milan, Italy; Dipartimento di Scienze Cliniche e Comunità, Università degli Studi di Milano, Milan, Italy.
  3. PhD program in Neuroscience, Università degli Studi di Milano-Bicocca, Monza, Italy; Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
  4. Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy.
  5. Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi" (INGM), Milan, Italy.
  6. Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi" (INGM), Milan, Italy; Dipartimento di Bioscienze, Università degli Studi di Milano, Milan, Italy.
  7. Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
  8. Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy; IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
  9. Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milan, Italy. Electronic address: [email protected].

PMID: 34214631 DOI: 10.1016/j.phrs.2021.105750

Abstract

Duchenne muscular dystrophy (DMD) causes progressive skeletal muscle degeneration and currently there are few therapeutic options. The identification of new drug targets and their validation in model systems of DMD could be a promising approach to make progress in finding new treatments for this lethal disease. Histone deacetylases (HDACs) play key roles in myogenesis and the therapeutic approach targeting HDACs in DMD is in an advanced phase of clinical trial. Here, we show that the expression of HDAC8, one of the members of the HDAC family, is increased in DMD patients and dystrophic zebrafish. The selective inhibition of HDAC8 with the PCI-34051 inhibitor rescues skeletal muscle defects, similarly to the treatment with the pan-HDAC inhibitor Givinostat. Through acetylation profile of zebrafish with HDAC8 dysregulation, we identified new HDAC8 targets involved in cytoskeleton organization such as tubulin that, when acetylated, is a marker of stable microtubules. Our work provides evidence of HDAC8 overexpression in DMD patients and zebrafish and supports its specific inhibition as a new valuable therapeutic approach in the treatment of this pathology.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Keywords: Duchenne muscular dystrophy; Givinostat; Givinostat Hydrochloride Hydrate (PubChem CID: 9804991); HDAC8; PCI-34051; PCI-34051 (PubChem CID:24753719); Zebrafish

Publication Types