Matches in SemOpenAlex for { <https://semopenalex.org/work/W2980759717> ?p ?o ?g. }
Showing items 1 to 83 of
83
with 100 items per page.
- W2980759717 abstract "We previously found that three neutrophil granule proteins with similar structures: the cationic antimicrobial protein of 37 kDa (CAP37), neutrophil elastase (NE), and cathepsin G (CG) cleave Aβ and interact with the receptor for advanced glycation end-products (RAGE). Since soluble oligomer and fibril aggregates are the most toxic forms of Aβ in the brain, we investigated whether CAP37, NE, and CG could also inhibit the aggregation of Aβ and the direct toxicity of Aβ on neuronal cells. Aβ fibrillation was quantified using Thioflavin T in the presence of increasing concentrations of CAP37, NE, and CG. Enzymatic activities were quantified on Aβ substrate, and an efficient protease inhibitor was selected for each enzyme. Fibrillation experiments were then performed in the presence of saturating concentrations of selected protease inhibitors to determine if Aβ cleavage is necessary for the anti-fibrillation effect of each protein. Finally, toxicity of Aβ fibrils and oligomers prepared in the presence of increasing concentrations of CAP37, NE, and CG was measured on the mouse neuroblastoma cell line Neuro-2a, using Trypan blue to quantify cell death. All three proteins inhibit Aβ fibrillation in a dose-dependent manner with the following efficiencies: NE>CG>CAP37. Enzymatic activities and the contribution of Aβ cleavage to anti-fibrillation effects was NE>CG>CAP37. Aβ fibrils and oligomers killed respectively 35 and 70% of Neuro-2a cells in 24 h. Only NE and CG were able to significantly inhibit the neurotoxicity of these Aβ aggregates. Interestingly, CG was more efficient than NE in inhibiting the neurotoxicity of Aβ oligomers. CG displayed a level of protection against Aβ oligomers that could not be fully explained by cleavage of Aβ. We hypothesize that direct binding of CG to Aβ could also contribute to its inhibition of Aβ oligomerization. Our results suggest a protective role of neutrophil granule proteins in the brains of patients with AD. Our current focus is the development of therapeutic peptides derived from these proteins to mimic the effects of the full-length proteins for inhibition of Aβ aggregation and neurotoxicity, and inhibition of neuroinflammation through inactivation of RAGE." @default.
- W2980759717 created "2019-10-25" @default.
- W2980759717 creator A5039062180 @default.
- W2980759717 creator A5049663253 @default.
- W2980759717 creator A5057671024 @default.
- W2980759717 date "2019-07-01" @default.
- W2980759717 modified "2023-09-26" @default.
- W2980759717 title "P4-498: NEUTROPHIL GRANULE PROTEINS INHIBIT AMYLOID BETA AGGREGATION AND NEUROTOXICITY" @default.
- W2980759717 doi "https://doi.org/10.1016/j.jalz.2019.08.044" @default.
- W2980759717 hasPublicationYear "2019" @default.
- W2980759717 type Work @default.
- W2980759717 sameAs 2980759717 @default.
- W2980759717 citedByCount "0" @default.
- W2980759717 crossrefType "journal-article" @default.
- W2980759717 hasAuthorship W2980759717A5039062180 @default.
- W2980759717 hasAuthorship W2980759717A5049663253 @default.
- W2980759717 hasAuthorship W2980759717A5057671024 @default.
- W2980759717 hasBestOaLocation W29807597171 @default.
- W2980759717 hasConcept C12554922 @default.
- W2980759717 hasConcept C126322002 @default.
- W2980759717 hasConcept C157207234 @default.
- W2980759717 hasConcept C178790620 @default.
- W2980759717 hasConcept C181199279 @default.
- W2980759717 hasConcept C182220744 @default.
- W2980759717 hasConcept C185592680 @default.
- W2980759717 hasConcept C203014093 @default.
- W2980759717 hasConcept C204232928 @default.
- W2980759717 hasConcept C27523624 @default.
- W2980759717 hasConcept C2776156579 @default.
- W2980759717 hasConcept C2777132095 @default.
- W2980759717 hasConcept C2777356233 @default.
- W2980759717 hasConcept C2778896982 @default.
- W2980759717 hasConcept C2779134260 @default.
- W2980759717 hasConcept C2779161974 @default.
- W2980759717 hasConcept C2779281246 @default.
- W2980759717 hasConcept C2779491297 @default.
- W2980759717 hasConcept C29730261 @default.
- W2980759717 hasConcept C502032728 @default.
- W2980759717 hasConcept C55493867 @default.
- W2980759717 hasConcept C71924100 @default.
- W2980759717 hasConcept C86803240 @default.
- W2980759717 hasConceptScore W2980759717C12554922 @default.
- W2980759717 hasConceptScore W2980759717C126322002 @default.
- W2980759717 hasConceptScore W2980759717C157207234 @default.
- W2980759717 hasConceptScore W2980759717C178790620 @default.
- W2980759717 hasConceptScore W2980759717C181199279 @default.
- W2980759717 hasConceptScore W2980759717C182220744 @default.
- W2980759717 hasConceptScore W2980759717C185592680 @default.
- W2980759717 hasConceptScore W2980759717C203014093 @default.
- W2980759717 hasConceptScore W2980759717C204232928 @default.
- W2980759717 hasConceptScore W2980759717C27523624 @default.
- W2980759717 hasConceptScore W2980759717C2776156579 @default.
- W2980759717 hasConceptScore W2980759717C2777132095 @default.
- W2980759717 hasConceptScore W2980759717C2777356233 @default.
- W2980759717 hasConceptScore W2980759717C2778896982 @default.
- W2980759717 hasConceptScore W2980759717C2779134260 @default.
- W2980759717 hasConceptScore W2980759717C2779161974 @default.
- W2980759717 hasConceptScore W2980759717C2779281246 @default.
- W2980759717 hasConceptScore W2980759717C2779491297 @default.
- W2980759717 hasConceptScore W2980759717C29730261 @default.
- W2980759717 hasConceptScore W2980759717C502032728 @default.
- W2980759717 hasConceptScore W2980759717C55493867 @default.
- W2980759717 hasConceptScore W2980759717C71924100 @default.
- W2980759717 hasConceptScore W2980759717C86803240 @default.
- W2980759717 hasIssue "7S_Part_29" @default.
- W2980759717 hasLocation W29807597171 @default.
- W2980759717 hasOpenAccess W2980759717 @default.
- W2980759717 hasPrimaryLocation W29807597171 @default.
- W2980759717 hasRelatedWork W1484929409 @default.
- W2980759717 hasRelatedWork W2001923760 @default.
- W2980759717 hasRelatedWork W2007603595 @default.
- W2980759717 hasRelatedWork W2010121181 @default.
- W2980759717 hasRelatedWork W2032840656 @default.
- W2980759717 hasRelatedWork W2063226724 @default.
- W2980759717 hasRelatedWork W2386887887 @default.
- W2980759717 hasRelatedWork W2980759717 @default.
- W2980759717 hasRelatedWork W3024733534 @default.
- W2980759717 hasRelatedWork W4306725349 @default.
- W2980759717 hasVolume "15" @default.
- W2980759717 isParatext "false" @default.
- W2980759717 isRetracted "false" @default.
- W2980759717 magId "2980759717" @default.
- W2980759717 workType "article" @default.