Despite its roles in innate immunity, the importance of MPO in preventing infection is unclear, as individuals with MPO deficiency are asymptomatic with the exception of an increased risk of candidiasis.
Here, we produced hematologic chimerism in the 5XFAD mouse model of AD, with MPO deficient mice, resulting in 5XFAD with hematologic MPO deficiency (5XFAD-MPO KO).
The <sup>18</sup>F-MAPP PET imaging noninvasively differentiated varying amounts of MPO activity, competitive inhibition, and MPO deficiency in living animals, confirming specificity and showing that the radioprobe can quantify changes in in vivo MPO activity.
Therefore, MPO inhibition with ABAH or MPO deficiency creates a protective environment that decreased inflammatory cell recruitment and increased expression of survival factors to improve functional outcome.
In addition, application of the analytical tools of cell and molecular biology has allowed definition of specific genotypes underlying MPO deficiency and the impact of particular mutations on the fate of MPO precursors along the biosynthetic pathway.
We identified a novel missense mutation in the MPO gene at codon 173 whereby tyrosine is replaced with cysteine (Y173C) that is associated with MPO deficiency and assessed its impact on MPO processing and targeting in transfectants expressing normal or mutant proteins.
We identified a novel missense mutation in the MPO gene at codon 173 whereby tyrosine is replaced with cysteine (Y173C) that is associated with MPO deficiency and assessed its impact on MPO processing and targeting in transfectants expressing normal or mutant proteins.
We conclude from these studies that (a) hereditary MPO deficiency is not associated with a major deletion or rearrangement of the MPO gene; (b) myeloid precursors in an MPO-deficient individual contain normal amounts of an mRNA that is the same size as that for MPO in normal individuals; and (c) the genetic basis for MPO deficiency may be heterogeneous, with at least two genotypes generating the same phenotype.
Although the contribution of myeloperoxidase to the chemiluminescence assay has been noted, the possible diagnostic confusion between chronic granulomatous disease of childhood (which is rare and severe) and myeloperoxidase deficiency (which is common and of little clinical consequence) has not been stressed.
In close relatives of the patient, MPO values were found to be diminshed to a greater or lesser degree, thus suggesting variable expressivity of the heterozygote state of MPO deficiency.
Together, these results indicate a substantial involvement of neutrophil-derived MPO in the pathology of 5XFAD model of AD and suggest MPO as a potential therapeutic target in AD.
We studied the cellular localization of MPO and compared numbers of MPO cells in various brain regions between neurologically healthy individuals and patients with Parkinson's disease (PD) or Alzheimer's disease (AD; n = 10-25).