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Open Access 01-07-2016 | SSIEM 2015

Sirtuin activation as a therapeutic approach against inborn errors of metabolism

Authors: Jeannette C. Bleeker, Riekelt H. Houtkooper

Published in: Journal of Inherited Metabolic Disease | Issue 4/2016

Abstract

Protein acylation has emerged as a large family of post translational modifications in which an acyl group can alter the function of a wide variety of proteins, especially in response to metabolic stress. The acylation state is regulated through reversible acylation/deacylation. Acylation occurs enzymatically or non-enzymatically, and responds to acyl-CoA levels. Deacylation on the other hand is controlled through the NAD⁺-dependent sirtuin proteins. In several inborn errors of metabolism (IEMs), accumulation of acyl-CoAs, due to defects in amino acid and fatty acid metabolic pathways, can lead to hyperacylation of proteins. This can have a direct effect on protein function and might play a role in pathophysiology. In this review we describe several mouse and cell models for IEM that display high levels of lysine acylation. Furthermore, we discuss how sirtuins serve as a promising therapeutic target to restore acylation state and could treat IEMs. In this context we examine several pharmacological sirtuin activators, such as resveratrol, NAD⁺ precursors and PARP and CD38 inhibitors.

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Title: Sirtuin activation as a therapeutic approach against inborn errors of metabolism
Authors: Jeannette C. Bleeker
Riekelt H. Houtkooper
Publication date: 01-07-2016
Publisher: Springer Netherlands
Published in: Journal of Inherited Metabolic Disease / Issue 4/2016
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-016-9939-8

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