Journal article
Histone acetylation inhibitors promote axon growth in adult dorsal root ganglia neurons
Journal of neuroscience research, v 93(8), pp 1215-1228
Aug 2015
PMID: 25702820
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Intrinsic mechanisms that guide damaged axons to regenerate following spinal cord injury remain poorly understood. Manipulation of posttranslational modifications of key proteins in mature neurons could reinvigorate growth machinery after injury. One such modification is acetylation, a reversible process controlled by two enzyme families, the histone deacetylases (HDACs) and the histone acetyl transferases (HATs), acting in opposition. Whereas acetylated histones in the nucleus are associated with upregulation of growth-promoting genes, deacetylated tubulin in the axoplasm is associated with more labile microtubules, conducive to axon growth. This study investigates the effects of HAT and HDAC inhibitors on cultured adult dorsal root ganglia (DRG) neurons and shows that inhibition of HATs by anacardic acid or CPTH2 improves axon outgrowth, whereas inhibition of HDACs by TSA or tubacin inhibits axon growth. Anacardic acid increased the number of axons able to cross an inhibitory chondroitin sulfate proteoglycan border. Histone acetylation but not tubulin acetylation level was affected by HAT inhibitors, whereas tubulin acetylation levels were increased in the presence of the HDAC inhibitor tubacin. Although the microtubule-stabilizing drug taxol did not have an effect on the lengths of DRG axons, nocodazole decreased axon lengths. Determining the mechanistic basis will require future studies, but this study shows that inhibitors of HAT can augment axon growth in adult DRG neurons, with the potential of aiding axon growth over inhibitory substrates produced by the glial scar.
Metrics
Details
- Title
- Histone acetylation inhibitors promote axon growth in adult dorsal root ganglia neurons
- Creators
- Shen Lin - Department of Neuroscience, Shriners Hospitals for Pediatric Research Center, Temple University, Philadelphia, PennsylvaniaKutaiba Nazif - Department of Neuroscience, Shriners Hospitals for Pediatric Research Center, Temple University, Philadelphia, PennsylvaniaAlexander Smith - Department of Neuroscience, Shriners Hospitals for Pediatric Research Center, Temple University, Philadelphia, PennsylvaniaPeter W Baas - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PennsylvaniaGeorge M Smith - Department of Neuroscience, Shriners Hospitals for Pediatric Research Center, Temple University, Philadelphia, Pennsylvania
- Publication Details
- Journal of neuroscience research, v 93(8), pp 1215-1228
- Publisher
- Wiley; United States
- Grant note
- R01 NS060784 / NINDS NIH HHS NS060784 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000356675600005
- Scopus ID
- 2-s2.0-84931572525
- Other Identifier
- 991014877676204721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences