FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2283000001> ?p ?o ?g. }

• W2283000001 abstract "Post mortem investigations of brains from patients with AD revealed a markedly down regulated expression IGF-1R, and insulin receptor substrate (IRS) proteins, and these changes progress with severity of neurodegeneration. A common feature in neurons from AD patients is a downregulation of IGF-1R. To investigate the role of neuronal IGF-1R signaling in AD neuron-specific IGF-1R (nIGF-1R-/-) deficient mice were generated. These mice were crossed with mice expressing the Swedish mutation of human APP695 harbouring the double mutation Lys670→; Asn, Met671→; Leu which was found in a Swedish family with early-onset AD (APPsw, Tg2576 mice). nIGF-1R-/- mice were generated using the cre-loxP-system under the control of the neuron-specific synapsin-1 promoter and crossed them into the Tg2576 background. The offsprings of these mice (WT, Tg2576, nIGF-1R-/-, nIGF-1R-/-Tg2576) were analysed at two different time points. Kaplan-Meier analysis, amyloid accumulation as well as metabolic and somatic factors of the offspring were investigated during an observation period of 60 weeks. Western blot analysis of isolated hippocampi displayed a 40% reduced IGF-1R expression in nIGF-1R-/- and nIGF-1R-/-Tg2576 compared to WT and Tg2576 animals, whereas other brain regions e.g. cortex or cerebellum did not show significant IGF-1R deletion. Thus, conditional IGF-1R deletion using Cre recombinase expression under the control of the synapsin-1 promoter leads to a hippocampus-specific downregulation of IGF-1R. Further analysis of Cre recombinase expression in a lacZ reporter mouse strain revealed a Cre recombinase activity driven by the synapsin-1 promoter in the dentus gyrus and the CA3 region of the hippocampus. Kaplan-Meier-analysis revealed a 60% mortality of Tg2576 mice after 60 weeks of observation. In contrast nIGF-1R-/-Tg2576 were protected against premature mortality of Tg2576 mice (p&≤0.02; Tg2576 vs. nIGF-1R-/-Tg2576). Isolated hippocampi of 28 and 60 weeks old nIGF-1R-/-Tg2576 animals showed a 50% reduced Aβ1-40 and Aβ1-42 accumulation compared to Tg2576. Additionally, APP α- and β-C-terminal fragments were reduced in hippocampi of nIGF-1R-/-Tg2576 compared Tg2576 mice due to a modification of α- and β-secretases activity. In addition Aβ plaque burden was reduced in Tg2576 animals with neuronal IGF-1R deletion. Taken together the results of the present thesis demonstrate that decreased neuronal IGF-1R signaling predominantly in the hippocampus protects against APPsw induced mortality. Moreover IGF-1R mediated signals influence APP processing due to a modification of α- and β-secretases leading to reduced Aβ accumulation and amyloid plaque burden. Thus, downregulation of IGF-1R observed in neurons of patients suffering from Alzheimer's disease is most likely a compensatory phenomenon to decrease amyloid accumulation and prolong survival." @default.
• W2283000001 created "2016-06-24" @default.
• W2283000001 creator A5091200940 @default.
• W2283000001 date "2009-01-01" @default.
• W2283000001 modified "2023-09-24" @default.
• W2283000001 title "Role of neuronal IGF-1R signaling for the pathogenesis of Alzheimer's disease" @default.
• W2283000001 hasPublicationYear "2009" @default.
• W2283000001 type Work @default.
• W2283000001 sameAs 2283000001 @default.
• W2283000001 citedByCount "0" @default.
• W2283000001 crossrefType "dissertation" @default.
• W2283000001 hasAuthorship W2283000001A5091200940 @default.
• W2283000001 hasConcept C102230213 @default.
• W2283000001 hasConcept C104317684 @default.
• W2283000001 hasConcept C125929170 @default.
• W2283000001 hasConcept C126322002 @default.
• W2283000001 hasConcept C127561419 @default.
• W2283000001 hasConcept C130316041 @default.
• W2283000001 hasConcept C134018914 @default.
• W2283000001 hasConcept C141035611 @default.
• W2283000001 hasConcept C148785051 @default.
• W2283000001 hasConcept C153911025 @default.
• W2283000001 hasConcept C2776925932 @default.
• W2283000001 hasConcept C2779134260 @default.
• W2283000001 hasConcept C41625074 @default.
• W2283000001 hasConcept C50493954 @default.
• W2283000001 hasConcept C54355233 @default.
• W2283000001 hasConcept C71924100 @default.
• W2283000001 hasConcept C86803240 @default.
• W2283000001 hasConceptScore W2283000001C102230213 @default.
• W2283000001 hasConceptScore W2283000001C104317684 @default.
• W2283000001 hasConceptScore W2283000001C125929170 @default.
• W2283000001 hasConceptScore W2283000001C126322002 @default.
• W2283000001 hasConceptScore W2283000001C127561419 @default.
• W2283000001 hasConceptScore W2283000001C130316041 @default.
• W2283000001 hasConceptScore W2283000001C134018914 @default.
• W2283000001 hasConceptScore W2283000001C141035611 @default.
• W2283000001 hasConceptScore W2283000001C148785051 @default.
• W2283000001 hasConceptScore W2283000001C153911025 @default.
• W2283000001 hasConceptScore W2283000001C2776925932 @default.
• W2283000001 hasConceptScore W2283000001C2779134260 @default.
• W2283000001 hasConceptScore W2283000001C41625074 @default.
• W2283000001 hasConceptScore W2283000001C50493954 @default.
• W2283000001 hasConceptScore W2283000001C54355233 @default.
• W2283000001 hasConceptScore W2283000001C71924100 @default.
• W2283000001 hasConceptScore W2283000001C86803240 @default.
• W2283000001 hasLocation W22830000011 @default.
• W2283000001 hasOpenAccess W2283000001 @default.
• W2283000001 hasPrimaryLocation W22830000011 @default.
• W2283000001 hasRelatedWork W1686913959 @default.
• W2283000001 hasRelatedWork W1964312788 @default.
• W2283000001 hasRelatedWork W1993406797 @default.
• W2283000001 hasRelatedWork W1995856801 @default.
• W2283000001 hasRelatedWork W2006016322 @default.
• W2283000001 hasRelatedWork W2016312856 @default.
• W2283000001 hasRelatedWork W2023434583 @default.
• W2283000001 hasRelatedWork W2030782357 @default.
• W2283000001 hasRelatedWork W2070002301 @default.
• W2283000001 hasRelatedWork W20795525 @default.
• W2283000001 hasRelatedWork W2148723333 @default.
• W2283000001 hasRelatedWork W2151549304 @default.
• W2283000001 hasRelatedWork W2224688280 @default.
• W2283000001 hasRelatedWork W2360632295 @default.
• W2283000001 hasRelatedWork W2382371642 @default.
• W2283000001 hasRelatedWork W2462890524 @default.
• W2283000001 hasRelatedWork W2900373846 @default.
• W2283000001 hasRelatedWork W2965155693 @default.
• W2283000001 hasRelatedWork W3032885111 @default.
• W2283000001 hasRelatedWork W3164370414 @default.
• W2283000001 isParatext "false" @default.
• W2283000001 isRetracted "false" @default.
• W2283000001 magId "2283000001" @default.
• W2283000001 workType "dissertation" @default.