Systemic inflammation elevates cytosolic prolyl oligopeptidase protein expression but not peptidase activity in the cerebral cortices of familial Alzheimer`s disease modeling mice

Abstract

Changes in brain prolyl oligopeptidase (PREP) expression and activity have been associated with neuroinflammation and Alzheimer`s disease (AD). The role of PREP in AD, which onset can be contributed by peripheral infection-induced inflammation, is unknown. The aim of the study was to elucidate further the association of PREP with AD pathology and inflammation. Here, we quantitated PREP protein expression by liquid chromatography-tandem mass spectrometry-based quantitative targeted absolute proteomics and determined PREP peptidase activity in the cerebral cortices of familial AD (APdE9) and lipopolysaccharide (LPS)-induced inflammation mouse models. PREP activity was investigated using the fluorogenic substrate Suc-Gly-Pro-AMC. PREP expression was significantly increased (by 2-fold) in the brain cytosolic fraction of LPS treated APdE9 mice, while the peptidase activity remained unaltered. In the cortical crude membrane fraction, the PREP expression and activity were decreased by 35–40% in the LPS treated APdE9 mice. In conclusion, cortical cytosolic and membrane-bound PREP expression levels and enzyme activities were altered due to LPS-induced inflammation in the AD mouse model. Since the cytosolic protein expression increased without any concomitant increase in the peptidase activity, it is likely that PREP activity is affected by other factors than protein expression alone.

Keywords

• Alzheimer's disease
• Prolyl oligopeptidase
• Lipopolysaccharide
• Amyloid-β
• Mouse