FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3195680289> ?p ?o ?g. }

• W3195680289 abstract "Abstract Neprilysin (NEP) and insulin-degrading enzyme (IDE) are considered the two major catabolic enzymes that degrade amyloid β peptide (Aβ), the primary cause of Alzheimer’s disease (AD). However, their roles in Aβ metabolism in vivo have never been compared in an impartial and side-by-side manner. Here, we crossbred single App knock-in mice with NEP ( Mme ) KO mice and with IDE ( Ide ) KO mice to generate double mutants that were analyzed for their biochemical and Aβ pathology properties. We found that NEP is responsible for the metabolism of amyloidogenic insoluble Aβ whereas IDE affects soluble Aβ. A deficiency of NEP, but not of IDE, augmented the formation of Aβ plaques, dystrophic neurites, and astrocytic and microglial activation, all of which are key pathological events in the development of AD. In addition, a deficiency of NEP had no significant impact on the levels of various neuropeptides (somatostatin, substance P, cholecystokinin, and neuropeptide Y), well known to be in vitro substrates for NEP, presumably because NEP is expressed in secretory vesicles and on the presynaptic membranes of excitatory neurons while most if not all neuropeptides are secreted from inhibitory neurons. This argues against the concern that NEP up-regulation for treatment of preclinical AD would reduce the levels of these neuropeptides. These findings indicate that NEP relatively selectively degrades Aβ in the brain. Whereas familial AD (FAD) is unambiguously caused by an increased anabolism of Aβ, and of Aβ 42 and Aβ 43 in particular, the anabolism of Aβ appears unaffected before its deposition in the brain that subsequently leads to the onset of sporadic AD (SAD). These observations thus suggest that NEP-sensitive amyloidogenic Aβ likely plays a primary pathogenic role in the etiology of SAD. Our findings are consistent with the aging-dependent decline of NEP expression in human brain and with recent genome-wide association studies (GWAS) indicating that variants of the gene encoding NEP ( MME ) are associated with the risk of SAD development. Taken together, our results imply that the aging-associated decrease in NEP expression is a primary cause of SAD and could thus be a target for the treatment of preclinical AD once other factors such as apolipoprotein E genotypes have also been considered." @default.
• W3195680289 created "2021-08-30" @default.
• W3195680289 creator A5006383727 @default.
• W3195680289 creator A5007957055 @default.
• W3195680289 creator A5013301564 @default.
• W3195680289 creator A5018378610 @default.
• W3195680289 creator A5022394598 @default.
• W3195680289 creator A5023317571 @default.
• W3195680289 creator A5029037864 @default.
• W3195680289 creator A5029357813 @default.
• W3195680289 creator A5036678039 @default.
• W3195680289 creator A5041543448 @default.
• W3195680289 creator A5054125651 @default.
• W3195680289 creator A5063921984 @default.
• W3195680289 creator A5071488040 @default.
• W3195680289 creator A5088400958 @default.
• W3195680289 creator A5091908663 @default.
• W3195680289 date "2021-08-24" @default.
• W3195680289 modified "2023-09-26" @default.
• W3195680289 title "Neprilysin-sensitive amyloidogenic Aβ versus IDE-sensitive soluble Aβ: a probable mechanistic cause for sporadic Alzheimer’s disease" @default.
• W3195680289 cites W1544396872 @default.
• W3195680289 cites W1585511281 @default.
• W3195680289 cites W1602872921 @default.
• W3195680289 cites W1966734666 @default.
• W3195680289 cites W1971222486 @default.
• W3195680289 cites W1971855284 @default.
• W3195680289 cites W1979369962 @default.
• W3195680289 cites W1979912064 @default.
• W3195680289 cites W1989252530 @default.
• W3195680289 cites W1994890528 @default.
• W3195680289 cites W1998208719 @default.
• W3195680289 cites W1999319209 @default.
• W3195680289 cites W2002581515 @default.
• W3195680289 cites W200566656 @default.
• W3195680289 cites W2006802243 @default.
• W3195680289 cites W2006909079 @default.
• W3195680289 cites W2010996478 @default.
• W3195680289 cites W2013001343 @default.
• W3195680289 cites W2015708455 @default.
• W3195680289 cites W2029532449 @default.
• W3195680289 cites W2030011352 @default.
• W3195680289 cites W2032694200 @default.
• W3195680289 cites W2034933548 @default.
• W3195680289 cites W2034969383 @default.
• W3195680289 cites W2039481158 @default.
• W3195680289 cites W2051573772 @default.
• W3195680289 cites W2053983287 @default.
• W3195680289 cites W2056855059 @default.
• W3195680289 cites W2073364218 @default.
• W3195680289 cites W2076517751 @default.
• W3195680289 cites W2082185331 @default.
• W3195680289 cites W2083003238 @default.
• W3195680289 cites W2090150925 @default.
• W3195680289 cites W2090620788 @default.
• W3195680289 cites W2094794112 @default.
• W3195680289 cites W2114160207 @default.
• W3195680289 cites W2118482957 @default.
• W3195680289 cites W2129085204 @default.
• W3195680289 cites W2129337589 @default.
• W3195680289 cites W2130205752 @default.
• W3195680289 cites W2146955477 @default.
• W3195680289 cites W2150999725 @default.
• W3195680289 cites W2162275830 @default.
• W3195680289 cites W2171250577 @default.
• W3195680289 cites W2203955786 @default.
• W3195680289 cites W2329336071 @default.
• W3195680289 cites W2386517867 @default.
• W3195680289 cites W2472186754 @default.
• W3195680289 cites W2740213823 @default.
• W3195680289 cites W2885585289 @default.
• W3195680289 cites W2912213744 @default.
• W3195680289 cites W2940903529 @default.
• W3195680289 cites W3023726811 @default.
• W3195680289 cites W3044030235 @default.
• W3195680289 cites W3044641110 @default.
• W3195680289 cites W3080299178 @default.
• W3195680289 cites W3092171882 @default.
• W3195680289 cites W3092524884 @default.
• W3195680289 cites W3115346491 @default.
• W3195680289 cites W3119403831 @default.
• W3195680289 cites W3129189791 @default.
• W3195680289 cites W3161300359 @default.
• W3195680289 cites W3185712148 @default.
• W3195680289 cites W943620320 @default.
• W3195680289 doi "https://doi.org/10.1101/2021.08.22.457281" @default.
• W3195680289 hasPublicationYear "2021" @default.
• W3195680289 type Work @default.
• W3195680289 sameAs 3195680289 @default.
• W3195680289 citedByCount "1" @default.
• W3195680289 countsByYear W31956802892023 @default.
• W3195680289 crossrefType "posted-content" @default.
• W3195680289 hasAuthorship W3195680289A5006383727 @default.
• W3195680289 hasAuthorship W3195680289A5007957055 @default.
• W3195680289 hasAuthorship W3195680289A5013301564 @default.
• W3195680289 hasAuthorship W3195680289A5018378610 @default.
• W3195680289 hasAuthorship W3195680289A5022394598 @default.
• W3195680289 hasAuthorship W3195680289A5023317571 @default.
• W3195680289 hasAuthorship W3195680289A5029037864 @default.
• W3195680289 hasAuthorship W3195680289A5029357813 @default.
• W3195680289 hasAuthorship W3195680289A5036678039 @default.

• next