Quantification of murine brain samples to characterize the correlation between the LTA4H expression and aged-related neuroinflammation biomarkers

Abstract

The leukotriene A4 hydrolase (LTA4H) enzyme is implicated in age-related neuroinflammation, which may contribute to Alzheimer’s Disease (AD). LTA4H is an enzyme that plays a dual role in inflammation: 1) as an epoxide hydrolase (EH), LTA4H catalyzes the hydrolysis of leukotriene A4 (LTA4) to leukotriene B4 (LTB4) as an inflammatory response, and 2) as an aminopeptidase (AP), LTA4H catalyzes the hydrolysis of the tripeptide Pro-Gly-Pro (PGP) as an anti-inflammatory response. The two amino acid residues, Q136 and D375 are crucial for LTA4H activity. A mutation in Q136N demolished LTA4H AP activity while maintaining LTA4H EH activity, whereas a mutation in D375N had an exact opposite effect. For this study, we compared protein and lipid profiles in four groups of mice: young (less than 10 months), aged (over 18 months), LTA4H AP knockout, and LTA4H EH knockout. We utilized high resolution mass spectrometry technique to quantify LTA4H and other associated proteins in mice brain tissue. In addition, various lipid profiles associated with LTA4H were qualified with a lipidomics approach to detect inflammatory markers of, either AP pathway or EH pathway. We identified a significant difference in LTA4H expression between young and aged mice. This study will help support current literature suggesting neuroinflammation in AD.