Table I. The major targets and pathways shown to be altered by O-GlcNAc cycling in Neurodegenerative Disease.
The target, manipulation and cell type or organism are listed on the left. The basic finding and reference are in the two right panels. The Table is not an exhaustive compilation of the published literature but is meant to illustrate the approaches that have been taken
| Molecule/Protein | Agent Used | Tissue or cell line | Relevant result | Ref. |
|---|---|---|---|---|
| Tau | OGA inhibitor Thiamet-G | tau mutant (Pro301->Leu) mouse model of AD | Systemic administration of Thiamet-G reduced neurofibrillary tangles (NFT) | (Yuzwa et al., 2012) |
| Tau, APP | AD mouse model (TAPP) carrying tau (Pro301->Leu) and APP (APPSwe) mutations | Decreased tau phosphorylation and neurite plaques | (Yuzwa et al., 2014) | |
| Tau | Post mortem AD brain frontal cerebral cortex, and cerebellum | O-GlcNAc levels reduced | (Liu et al., 2004) | |
| Isolated proteins from AD patients brains | Normal tau entangles with hyperphosphorylated tau | (Alonso et al., 1996) | ||
| OGT Knockout mouse brain | Tau phosphorylation increased | (O’Donnell et al., 2004) | ||
| Tau, APP or polyglutamine expansion | C. elegans: OGT-1 and OGA-1 mutants | Neurodegeneration worsened in OGA-1 mutants, and ameliorated in OGT-1 mutant | (Wang et al., 2012) | |
| APP | SH-SY5Y neuroblastoma cells | O-GlcNAcylation induced α-secretase mediated cleavage of APP, resulting in neuroprotective sAPPα | (Jacobsen and Iverfeldt, 2011) | |
| Milton | Rat Hippocampal neurons | Increased O-GlcNAcylation decrease mitochondrial motility | (Pekkurnaz et al., 2014) | |
| Ogg1 | Murine neonatal cardiac myocytes | O-GlcNAcylation decreased Ogg1 activity that could lead to mDNA damage | (Cividini et al., 2016) | |
| MIBP1 | HEK293 cells | MIBP1 activity is suppressed by O-GlcNAcylation | (Iwashita et al., 2012) | |
| Electron Transport Chain (ETC) | Diabetic rat hearts | Increased O-GlcNAcylation could reduce ATP production by inhibiting the activity of ETC complexes | (Ma et al., 2016) | |
| TCA cycle enzymes | Diabetic rat hearts | Increased O-GlcNAc could reduce TCA activity | (Ma et al., 2016) | |
| Insulin Signaling Pathway | 3T3-L1 adipocytes | Increased O-GlcNAcylation inhibits insulin signaling pathway activation | (Vosseller et al., 2002) | |
| SNAP-29 | HeLa cells | Increased O-GlcNAcylation reduced autophagy by decreasing fusion between autophagosomes and endosome/lysosomes | (Guo et al., 2014) | |
| BCL2 | Diabetic db/db mice cardiomyocytes | (Marsh et al., 2013) | ||
| Atg7 | Mouse brain lysate | (Park et al., 2015) | ||
| α-synuclein | In vitro recombinant protein | O-GlcNAcylation prevents α-synuclein aggregation | (Marotta et al., 2015) | |
| Period | D. melanogaster | O-GlcNAcylation of regulate circadian timing by altering dPER subcellular localization | (Kim et al., 2012; Kaasik et al., 2013) | |
| KV7.3 (Kcnq3) | AgRP neurons in mouse | O-GlcNAcylation is essential for excitability of AgRP neurons by modifying Kcnq3 | (Ruan et al., 2014) |