Corn gluten meal peptides inhibit prolyl oligopeptidase and modulate ?-synuclein aggregation in KCl-treated SH-SY5Y cells

Prolyl oligopeptidase (POP) is known to be related to neurocognitive disorder as it degrades neuroactive pep-tides. POP inhibitory peptides from corn gluten meal hydrolysate (CGM-H) were identified and characterized. After a series of chromatographic separations, ALLTLSPLGPA was identified as the most effective POP inhibitor, with an IC50 value of 0.79 +/- 0.004 mM. Its in silico gastrointestinal (GI)-digested peptide, SPLGPA, exhibited 3-fold lower POP inhibitory activity, while higher inhibition was observed in SH-SY5Y cells when compared to its parent peptide. In addition, 25 mu M ALLTLSPLGPA notably reduced alpha-synuclein aggregation in KCl-treated SH-SY5Y cells. ALLTLSPLGPA and SPLGPA were characterized as mixed-type and uncompetitive inhibitors, respectively. They bound to POP via hydrogen bonds at the beta-propeller domain. These results demonstrated that peptides derived from CGM could have potential for developing nutraceutical products targeting brain health.