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Roles of O-GlcNAc in chronic diseases of aging
Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, MD, USA.
2016 (Engelska)Ingår i: Molecular Aspects of Medicine, ISSN 0098-2997, E-ISSN 1872-9452, Vol. 51, s. 1-15Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

O-GlcNAcylation, a dynamic nutrient and stress sensitive post-translational modification, occurs on myriad proteins in the cell nucleus, cytoplasm and mitochondria. O-GlcNAcylation serves as a nutrient sensor to regulate signaling, transcription, translation, cell division, metabolism, and stress sensitivity in all cells. Aberrant protein O-GlcNAcylation plays a critical role both in the development, as well as in the progression of a variety of age related diseases. O-GlcNAcylation underlies the etiology of diabetes, and changes in specific protein O-GlcNAc levels and sites are responsible for insulin expression and sensitivity and glucose toxicity. Abnormal O-GlcNAcylation contributes directly to diabetes related dysfunction of the heart, kidney and eyes and affects progression of cardiomyopathy, nephropathy and retinopathy. O-GlcNAcylation is a critical modification in the brain and plays a role in both plaque and tangle formation, thus making its study important in neurodegenerative disorders. O-GlcNAcylation also affects cellular growth and metabolism during the development and metastasis of cancer. Finally, alterations in O-GlcNAcylation of transcription factors in macrophages and lymphocytes affect inflammation and cytokine production. Thus, O-GlcNAcylation plays key roles in many of the major diseases associated with aging. Elucidation of its specific functions in both normal and diseased tissues is likely to uncover totally novel avenues for therapeutic intervention.

Ort, förlag, år, upplaga, sidor
Elsevier, 2016. Vol. 51, s. 1-15
Nyckelord [en]
O-GlcNAc, Hyperglycemia, Diabetes, Neurodegenerative disease, Cancer, Hexosamine biosynthetic pathway, O-GlcNAc transferase, O-GlcNAcase
Nationell ämneskategori
Gerontologi, medicinsk/hälsovetenskaplig inriktning
Identifikatorer
URN: urn:nbn:se:umu:diva-182713DOI: 10.1016/j.mam.2016.05.005ISI: 000384954900001PubMedID: 27259471Scopus ID: 2-s2.0-84973161413OAI: oai:DiVA.org:umu-182713DiVA, id: diva2:1548793
Tillgänglig från: 2021-05-03 Skapad: 2021-05-03 Senast uppdaterad: 2021-05-04Bibliografiskt granskad

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Lagerlöf, Olof

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Molecular Aspects of Medicine
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