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IP-LC-MSMS Enables Identification of Three Tau O-GlcNAcylation Sites as O-GlcNAcase Inhibition Pharmacodynamic Readout in Transgenic Mice Overexpressing Human Tau

Bijttebier S, Rodrigues Martins D, Mertens L, Grauwen K, Bruinzeel W, Willems R, Bartolomé-Nebreda JM, Theunis C, Bretteville A, Ebneth A, Dillen L.

Journal of Proteome Research - Published online 8 March 2023
DOI: 10.1021/acs.jproteome.2c00822
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O-GlcNAc modification forces the formation of an α-Synuclein amyloid-strain with notably diminished seeding activity and pathology

Balana AT , Mahul-Mellier AL, Nguyen BA , Horvath M, Javed A, Hard E R, Jasiqi Y, Singh P, Afrin S, Pedretti R, Singh V, Lee V MY , Luk KC, Saelices , Lashuel HA , Pratt MR

doi: https://doi.org/10.1101/2023.03.07.531573

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O-GlcNAcase Inhibitor ASN90 is a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies 

Permanne B, Sand A, Ousson S, Nény M, Hantson J, Schubert R, Wiessner C, Quattropani A, Beher*

ACS Chem. Neurosci. 2022, 13, 8, 1296–1314
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Current directions in tau research: Highlights from Tau 2020

Sexton C, Snyder H, Beher D, Boxer A, Brannelly P, Brion JP, Buée L, Cacace A, Chételat G, Citron M, DeVos S, Diaz K, Feldman H, Frost B, Goate A, Gold M, Hyman B, Johnson K, Karch C, Kerwin D, Koroshetz W, Litvan I, Morris H, Mummery C, Mutamba J, Patterson M, Quiroz Y, Rabinovici G, Rommel A, Shulman M, Toledo-Sherman L, Weninger S, Wildsmith K, Worley S, Carrillo M.

Alzheimer’s Dement. 2021;1-20.
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O-GlcNAcylation regulates dopamine neuron function, survival and degeneration in Parkinson disease.

Lee BE, Kim HY, Kim HJ, Jeong H, Kim BG, Lee HE, Lee J, Kim HB, Lee SE, Yang YR, Yi EC, Hanover JA, Myung K, Suh PG, Kwon T, Kim JI.

Brain. 2020 Dec 1;143(12):3699-3716.
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Inhibition of O-GlcNAcase leads to elevation of O-GlcNAc tau and reduction of tauopathy and cerebrospinal fluid tau in rTg4510 mice.

Hastings NB, Wang X, Song L, Butts BD, Grotz D, Hargreaves R, Fred Hess J, Hong KK, Huang CR, Hyde L, Laverty M, Lee J, Levitan D, Lu SX, Maguire M, Mahadomrongkul V, McEachern EJ, Ouyang X, Rosahl TW, Selnick H, Stanton M, Terracina G, Vocadlo DJ, Wang G, Duffy JL, Parker EM, Zhang L.

Mol Neurodegener. 2017 May 18;12(1):39.
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Increased O-GlcNAcylation reduces pathological tau without affecting its normal phosphorylation in a mouse model of tauopathy.

Graham DL, Gray AJ, Joyce JA, Yu D, O'Moore J, Carlson GA, Shearman MS, Dellovade TL, Hering H.

Neuropharmacology. 2014 Apr;79:307-13.
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Generation and characterization of a rabbit monoclonal antibody site-specific for tau O-GlcNAcylated at serine 400.

Cameron A, Giacomozzi B, Joyce J, Gray A, Graham D, Ousson S, Neny M, Beher D, Carlson G, O'Moore J, Shearman M, Hering H.

FEBS Lett. 2013 Nov; 586 (22): 3722 - 28
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Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation.

Yuzwa SA, Shan X, Macauley MS, Clark T, Skorobogatko Y, Vosseller K, Vocadlo DJ.

Nat Chem Biol. 2012 Feb 26;8(4):393-9.
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