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Antizyme Inhibitors in Polyamine Metabolism and Beyond: Physiopathological Implications

Polyamine Homeostasis in Snyder-Robinson Syndrome

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA
The Greenwood Genetic Center, Greenwood, SC 29646, USA
Author to whom correspondence should be addressed.
Med. Sci. 2018, 6(4), 112;
Received: 15 November 2018 / Revised: 29 November 2018 / Accepted: 3 December 2018 / Published: 7 December 2018
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, SMS deficiency causes a lack of spermine with an accumulation of spermidine. As polyamines, spermine, and spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell growth, differentiation, and survival. Using patient-derived lymphoblast cell lines, we sought to comprehensively investigate the effects of SMS deficiency on polyamine homeostatic mechanisms including polyamine biosynthetic and catabolic enzymes, derivatives of the natural polyamines, and polyamine transport activity. In addition to decreased spermine and increased spermidine in SRS cells, ornithine decarboxylase activity and its product putrescine were significantly decreased. Treatment of SRS cells with exogenous spermine revealed that polyamine transport was active, as the cells accumulated spermine, decreased their spermidine level, and established a spermidine-to-spermine ratio within the range of wildtype cells. SRS cells also demonstrated elevated levels of tissue transglutaminase, a change associated with certain neurodegenerative diseases. These studies form a basis for further investigations into the leading biochemical changes and properties of SMS-mutant cells that potentially represent therapeutic targets for the treatment of Snyder-Robinson Syndrome. View Full-Text
Keywords: Snyder-Robinson Syndrome; spermine synthase; X-linked intellectual disability; polyamine transport; spermidine; spermine; transglutaminase Snyder-Robinson Syndrome; spermine synthase; X-linked intellectual disability; polyamine transport; spermidine; spermine; transglutaminase
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MDPI and ACS Style

Murray-Stewart, T.; Dunworth, M.; Foley, J.R.; Schwartz, C.E.; Casero, R.A., Jr. Polyamine Homeostasis in Snyder-Robinson Syndrome. Med. Sci. 2018, 6, 112.

AMA Style

Murray-Stewart T, Dunworth M, Foley JR, Schwartz CE, Casero RA Jr.. Polyamine Homeostasis in Snyder-Robinson Syndrome. Medical Sciences. 2018; 6(4):112.

Chicago/Turabian Style

Murray-Stewart, Tracy, Matthew Dunworth, Jackson R. Foley, Charles E. Schwartz, and Robert A. Casero Jr. 2018. "Polyamine Homeostasis in Snyder-Robinson Syndrome" Medical Sciences 6, no. 4: 112.

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