FTY720 Nanoformulation Induces O-GlcNacylation of Synuclein to Alleviate Synucleinopathy.

The post-translational modification and aggregation of alpha-synuclein are one of the major causes of Parkinson's disease (PD) regulation. In that, the phosphorylation and nitration of synuclein elevate the aggregation, while O-GlcNacylation prevents the aggregation of synuclein. The inhibition of synuclein aggregation directs the development of PD therapy. The endowed O-GlcNacylation of synuclein could be a promising strategy to inhibit synucleinopathy. Therefore, the neuroprotective chitosan-based FTY720 nanoformulation, PP2A (Protein phosphatase 2) activator has been employed to evaluate the PP2A role in the O-GlcNacylation of synuclein in an in vivo PD model. The neuroprotective effect of our nanoformulation is attributed to the upregulation of tyrosine hydroxylase (TH), the PD therapeutic target, with behavioral improvement in animals against rotenone-induced PD deficits. The neuroprotective molecular insights revealed the camouflaged role of PP2A by endowing the OGT activity that induces O-GlcNacylation of synuclein in the reduction of synucleinopathy.