The histone deacetylase class I, II inhibitor trichostatin A delays peripheral neurodegeneration.
J Mol Histol
; 50(2): 167-178, 2019 Apr.
Article
em En
| MEDLINE
| ID: mdl-30671879
ABSTRACT
Peripheral nerves, which consist of an axon and a unique glial cell called a Schwann cell, transduce signals from the brain and spinal cord to target organs. Peripheral nerve degeneration leads to distal motor or sensory disorders such as diabetic neuropathy, Charcot-Marie-Tooth disease, and Gullain-Barré syndrome, with symptoms such as dysesthesia, speech impairment, vision change, erectile dysfunction, and urinary incontinence. Schwann cells play an important role in peripheral nerve degeneration. Therefore, revealing the characteristics of Schwann cells will be essential in understanding peripheral neurodegeneration-related diseases for which there is currently no effective treatment. Trichostatin A (TSA) is a noncompetitive, reversible inhibitor of class I and II histone deacetylases (HDACs). HDACs have been shown not only to deacetylate histones but also to target non-histone proteins involved in diverse signaling pathways. Recent studies have revealed that diverse HDAC subtypes regulate peripheral neurodegeneration. Thus, regulating HDAC levels could be an effective strategy for the development of drugs targeting peripheral nerve-related diseases. In fact, the use of TSA has been investigated for the treatment of many diseases, including degenerative diseases of the central nervous system; however, the effects of TSA on peripheral neurodegeneration have not yet been well established. In this study, we revealed the effect of TSA on the process of peripheral neurodegeneration. TSA successfully inhibited myelin fragmentation, axonal degradation, and trans-dedifferentiation and proliferation of Schwann cells, which are essential phenotypes in peripheral neurodegeneration. Therefore, TSA could be a potential drug for patients suffering from peripheral neurodegeneration-related diseases.
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MEDLINE
Assunto principal:
Doenças do Sistema Nervoso Periférico
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Inibidores de Histona Desacetilases
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Ácidos Hidroxâmicos
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Degeneração Neural
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article