O-GlcNAc has been found to slow protein aggregation, though the generality of this phenomenon is unknown.
Solid-phase peptide synthesis was used to prepare full-length α-synuclein with an O-GlcNAc modification at T72. Thioflavin T aggregation assays and transmission electron microscopy demonstrated that this modified α-synuclein does not readily form aggregates.
Treatment of JNPL3 tau transgenic mice with an OGA inhibitor was shown to increase microtubule-associated protein tau O-GlcNAcylation. Immunohistochemistry analysis of the brainstem revealed decreased formation of neurofibrillary tangles. Recombinant O-GlcNAcylated tau was shown to aggregate slower than unmodified tau in an in vitro thioflavin S aggregation assay. Similar results were obtained for a recombinantly prepared O-GlcNAcylated TAB1 construct versus its unmodified form.