UNASSIGNED: One of the main characteristics of @entity195 ( @entity195 ) is the b-amyloid peptide (Ab) generated by b- and x03B3;-secretase processing of the @entity477 ( @entity477 ). Previously it has been demonstrated that @entity1474 ( @entity5204 ), especially @entity4600 ( @entity4601 ), are associated with a reduced risk of @entity195 caused by decreased Ab production. However, in epidemiological studies and nutritional approaches, the outcomes of @entity4601 -dependent treatment were partially controversial. @entity5204 are very susceptible to reactive @entity26 species and lipid peroxidation, which are increased during disease pathology. In line with published results, lipid peroxidation was elevated in @entity1 postmortem @entity195 brains; especially @entity11838 ( @entity13789 ) was increased. To investigate whether lipid peroxidation is only a consequence or might also influence the processes leading to @entity195 , we analyzed 7 different oxidized lipid species including 5 oxidized @entity4601 derivatives and the lipid peroxidation products of x03C9;-3 and x03C9;-6 @entity5204 , @entity13789 and @entity69071 , in @entity1 @entity521 cells and @entity19 mixed cortical neurons. In the presence of oxidized lipids Ab and soluble b-secreted @entity477 levels were elevated, whereas soluble a-secreted @entity477 was decreased, suggesting a shift from the nonamyloidogenic to the amyloidogenic pathway of @entity477 processing. Furthermore, b- and x03B3;-secretase activity was increased by oxidized lipids via increased gene expression and additionally by a direct effect on b-secretase activity. Importantly, only 1% oxidized @entity4601 was sufficient to revert the protective effect of @entity4601 and to significantly increase Ab production. Therefore, our results emphasize the need to prevent @entity4601 from oxidation in nutritional approaches and might help explain the divergent results of clinical @entity4601 studies.

Oxidized @entity4600 Species and Lipid Peroxidation Products Increase Amyloidogenic XXXX Processing.

@entity1 :: ('9606', 'Species') :: ['human'] @entity5204 :: ('CHEBI:26208', 'Chemical') :: ['PUFAs'] @entity4600 :: ('CHEBI:28125', 'Chemical') :: ['docosahexaenoic acid'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity13789 :: ('CHEBI:58968', 'Chemical') :: ['HNE'] @entity1474 :: ('MESH:D005231', 'Chemical') :: ['polyunsaturated fatty acids'] @entity477 :: ('351', 'Gene') :: ['APP', 'amyloid precursor protein'] @entity4601 :: ('CHEBI:16016', 'Chemical') :: ['DHA'] @entity69071 :: ('MESH:C063409', 'Chemical') :: ['4-hydroxy-hexenal'] @entity521 :: ('MESH:D009447', 'Disease') :: ['neuroblastoma'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', "Alzheimer's disease"] @entity11838 :: ('MESH:C027576', 'Chemical') :: ['4-hydroxy-nonenal']
@entity477 :: (351,Gene) :: ['Amyloid Precursor Protein']
