The Therapeutic Potential of HDAC Inhibitors in the Treatment of Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a devastating autoimmune disorder of the central nervous system (CNS) for which there is no efficacious cure. Thanks to numerous preclinical and clinical studies, drugs able to mitigate the inexorable course of the disease have been made available recently. Still, there is a terrible need for compounds capable of reducing the severity of the autoimmune attack and of blocking progression of the disorder. Also, besides the classic immunosuppressive strategies, it is now appreciated that compounds directly targeting neuronal death can be of relevance to the treatment of MS patients. Acetylation homeostasis is a key regulator of both immune cell activation and neuronal survival. Of note, potent histone deacetylase inhibitors (HDACi) endowed with antiinflammatory and neuroprotective properties have been identified. Efficacy of HDACi in experimental models of MS has been reported consistently. In this review, we provide an appraisal of the literature on HDACi and MS, also discussing the mechanisms by which HDACi can suppress the autoimmune attack to the CNS.

Acetate Supplementation as a Means of Inducing Glioblastoma Stem-Like Cell Growth Arrest

“…Numerous natural and synthetic products, including a broad range of dietary agents (e.g., short‐chain fatty acids sodium butyrate and sodium proprionate, genistein, quercetin, trichostatin A, sulforaphane, resveratrol, caffeine) exhibit HDAC inhibitory activity in vitro and/or in vivo (Myzak et al, ; Seidel et al, ). HDAC inhibition has also been considered a therapeutic approach for a number of neuropathologies, including neurodegenerative disorders (e.g., Alzheimer's disease, Huntington's disease, Parkinson's disease) (Konsoula and Barile, ), cerebral ischemia (Schweizer et al, ), acute central nervous system injury (Shein and Shohami, ; Moffett et al, ), neuropsychiatric disorders (Ariyannur et al, ), muscular dystrophies (Consalvi et al, ), and multiple sclerosis (Faraco et al, ). We acknowledge that GTA provides acetate globally; thus, we cannot target specific cells or proteins.…”

Expression Profiles of the Nuclear Receptors and Their Transcriptional Coregulators During Differentiation of Neural Stem Cells

“…Valproic acid, a compound frequently used as a mood stabilizer and as an anticonvulsant, is a HDAC inhibitor [42]. Further, several other HDAC inhibitors alter the fate of neural cells, and are now intensive research targets as potential therapeutic agents for several neurodegenerative diseases, cognitive disorders, multiple sclerosis and CNS trauma/injuries [39, 43 – 45]. Thus, it is quite interesting to elucidate the exact roles of HDAC subtypes on the functions/differentiation of NSCs.…”

Is there any therapeutic value for the use of histone deacetylase inhibitors for chronic pain?

“…The significant therapeutic potential of HDACIs as anti-inflammatory and immunosuppressive drugs was reported subsequently (Cantley and Haynes, 2013;Licciardi et al, 2013). Furthermore, HDACIs have been demonstrated to have therapeutic effects in various central nervous system pathologies, including multiple sclerosis (Faraco et al, 2011), Rett syndrome (Kazantsev and Thompson, 2008), brain ischemia (Formisano et al, 2015), Huntington's disease (Jia et al, 2015), and Parkinson's disease (Jin et al, 2014). As discussed above, HDACIs have also been shown to be effective analgesics.…”