O-GlcNAcylation as a Therapeutic Target for Alzheimer's Disease
Park, Jinsu Lai, Mitchell KP Arumugam, Thiruma V Jo, Dong-Gyu
Park, Jinsu
Jo, Dong-Gyu
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Abstract
Alzheimer’s disease (AD) is the most common cause of dementia and the number of elderly patients suffering from AD has been steadily increasing. Despite worldwide efforts to cope with this disease, little progress has been achieved with regard to identification of effective therapeutics. Thus, active research focusing on identification of new therapeutic targets of AD is ongoing. Among the new targets, post-translational modifications which modify the properties of mature proteins have gained attention. O-GlcNAcylation, a type of PTM that attaches O-linked β-N-acetylglucosamine (O-GlcNAc) to a protein, is being sought as a new target to treat AD pathologies. O-GlcNAcylation has been known to modify the two important components of AD pathological hallmarks, amyloid precursor protein, and tau protein. In addition, elevating O-GlcNAcylation levels in AD animal models has been shown to be effective in alleviating AD-associated pathology. Although studies investigating the precise mechanism of reversal of AD pathologies by targeting O-GlcNAcylation are not yet complete, it is clearly important to examine O-GlcNAcylation regulation as a target of AD therapeutics. This review highlights the mechanisms of O-GlcNAcylation and its role as a potential therapeutic target under physiological and pathological AD conditions.
Keywords
Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, Alzheimer's disease, O-GlcNAcylation, O-GlcNAc, Glucose metabolism, Neurodegeneration, LINKED N-ACETYLGLUCOSAMINE, AMYLOID PRECURSOR PROTEIN, FRUCTOSE 6-PHOSPHATE AMIDOTRANSFERASE, AMYOTROPHIC-LATERAL-SCLEROSIS, GAMMA-SECRETASE CLEAVAGE, TYPE-2 DIABETES-MELLITUS, BRAIN INSULIN-RESISTANCE, TRANSGENIC MOUSE MODEL, GLCNAC TRANSFERASE, PARKINSONS-DISEASE
Source Title
NEUROMOLECULAR MEDICINE
Publisher
HUMANA PRESS INC
Series/Report No.
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Date
2020-06-01
DOI
10.1007/s12017-019-08584-0
Type
Review