Proper neuronal development is essential to growth and adult brain function. Alterations at any step of this highly organized sequence of events, due to genetic mutations or environmental factors, triggers brain malformations, which are leading causes of diseases including epilepsy, intellectual disabilities, and many others. The role of glycosylation in neuronal development has been emphasized for many years, notably in studying human congenital disorders of glycosylation (CDGs). These diseases highlight that genetic defects in glycosylation pathways are almost always associated with severe neurological abnormalities, suggesting that glycosylation plays an essential role in early brain development. Congenital disorders of O-GlcNAcylation are no exception, and all mutations of the O-GlcNAc transferase (OGT) are associated with X-linked intellectual disabilities (XLID). In addition, mouse models and in vitro mechanistic studies have reinforced the essential role of O-GlcNAcylation in neuronal development and signaling. In this review, we give an overview of the role of O-GlcNAcylation in this critical physiological process and emphasize the consequences of its dysregulation.
Many dietary plants possess high levels of 18-carbon containing lipids from both omega-6 and omega-3 unsaturated fatty acids (e.g., linoleic and alpha-linolenic acid, respectively). These dietary lipids can be metabolized to lipid mediators collectively termed octadecanoids, which can in turn interact with immune cells (e.g., macrophages, eosinophils) to exert a number of potent biological effects. These octadecanoid lipid mediators have been little studied and represent an exciting new area of lipid biochemistry. For further information, see the review in this issue by Quaranta and colleagues (pages 1569–1582). Cover image credit: Emmanuelle Chevallier.
The O-GlcNAc cycling in neurodevelopment and associated diseases
Dawn M. Wenzel, Stephanie Olivier-Van Stichelen; The O-GlcNAc cycling in neurodevelopment and associated diseases. Biochem Soc Trans 16 December 2022; 50 (6): 1693–1702. doi: https://doi.org/10.1042/BST20220539
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