Clinical and Experimental Applications of Sodium Phenylbutyrate

Abstract

Histone acetyltransferase and histone deacetylase are enzymes responsible for histone acetylation and deacetylation, respectively, in which the histones are acetylated and deacetylated on lysine residues in the N-terminal tail and on the surface of the nucleosome core. These processes are considered the most important epigenetic mechanisms for remodeling the chromatin structure and controlling the gene expression. Histone acetylation is associated with gene activation. Sodium phenylbutyrate is a histone deacetylase inhibitor that has been approved for treatement of urea cycle disorders and is under investigation in cancer, hemoglobinopathies, motor neuron diseases, and cystic fibrosis clinical trials. Due to its characteristics, not only of histone deacetylase inhibitor, but also of ammonia sink and chemical chaperone, the interest towards this molecule is growing worldwide. This review aims to update the current literature, involving the use of sodium phenylbutyrate in experimental studies and clinical trials.

The effect of small molecules on nuclear-encoded translation diseases

“…SPB is a histone deacetylase inhibitor that promotes relief of endoplasmic reticulum stress. It has been approved for treatment of urea cycle disorders and is being investigated in cancer, motor neuron diseases, hemoglobinopathies and cystic fibrosis [55], diabetes [56] and familial hypercholesterolemia [57]. It has also been found to exert neuroprotective effects in mouse models of Parkinson's [58] and Alzheimer's diseases [59].…”

Sporadic inclusion-body myositis: A degenerative muscle disease associated with aging, impaired muscle protein homeostasis and abnormal mitophagy

“…NaPB is an orally bioavailable small molecule approved by the FDA for treatment of urea cycle-disorders [125,126]. Taken daily and longterm by infants, children and adults, it is usually well-tolerated [126].…”

“…Taken daily and longterm by infants, children and adults, it is usually well-tolerated [126]. NaPB reportedly mimics the function of intracellular molecular chaperones by preventing protein aggregation and oligomerization [127], in addition to being a histone deacetylase inhibitor [125,126].…”

Are epigenetic drugs for diabetes and obesity at our door step?

“…It is currently being tested in patients with recurrent malignant gliomas, hemoglobinopathies, motor neuron diseases, and cystic fibrosis. PBA can also act as a chemical chaperone [13].…”