FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2006802243> ?p ?o ?g. }

• W2006802243 endingPage "67" @default.
• W2006802243 startingPage "60" @default.
• W2006802243 abstract "Amyloid beta peptide (Aβ) is not only a major constituent of extracellular fibrillary pathologies in Alzheimer's disease (AD) brains, but is also physiologically produced and metabolized in neurons. This fact led us to the notion that an age-related decrease in Aβ catabolism may contribute to the molecular pathogenesis of AD, providing a rationale for seeking proteolytic enzymes that degrade Aβ in the brain. Our recent studies have demonstrated that neprilysin is the most potent Aβ-degrading enzyme in vivo. Deficiency of endogenous neprilysin elevates the level of Aβ in brains of neprilysin-knockout mice in a gene dose-dependent manner, and an age-associated decline of neprilysin occurs in several regions of mouse brain. Neuropathological alterations in these same regions have been implicated in cognitive impairments of AD patients at an early stage of the disease. Furthermore, the level of neprilysin mRNA has been found to be significantly and selectively reduced in the hippocampus and temporal cortex of AD patients. A clarification of the role played by decreased neprilysin activity in the pathogenesis of AD has opened up the possibility of neprilysin up-regulation as a novel preventive and therapeutic approach to AD. Since the expression level and activity of neprilysin are likely to be regulated by neuropeptides and their receptors, non-peptidic agonists for these receptors might be effective agents to maintain a sufficient level of Aβ catabolism in brains of the elderly. In addition to Aβ deposits, intraneuronal fibrillary lesions, such as neurofibrillary tangles, are also a pathological hallmark of AD, and the extent of the resultant cytoskeletal disruptions may be dependent upon the activity levels of proteolytic enzymes. Among proteases for which major cytoskeletal components are good substrates, calpains were shown to participate in excitotoxic stress-induced neuritic degeneration in our recent analysis using genetically engineered mice. Moreover, we have found that this pathology can be reduced by controlling the activity of an endogenous calpain inhibitor known as calpastatin, providing a possible approach for the treatment of diverse neurodegenerative disorders, including AD." @default.
• W2006802243 created "2016-06-24" @default.
• W2006802243 creator A5002819177 @default.
• W2006802243 creator A5023317571 @default.
• W2006802243 creator A5091908663 @default.
• W2006802243 date "2005-08-01" @default.
• W2006802243 modified "2023-10-18" @default.
• W2006802243 title "Understanding molecular mechanisms of proteolysis in Alzheimer's disease: Progress toward therapeutic interventions" @default.
• W2006802243 cites W141830102 @default.
• W2006802243 cites W1531666134 @default.
• W2006802243 cites W1967408430 @default.
• W2006802243 cites W1967464880 @default.
• W2006802243 cites W1967842104 @default.
• W2006802243 cites W1970684191 @default.
• W2006802243 cites W1970796584 @default.
• W2006802243 cites W1971855284 @default.
• W2006802243 cites W1979369962 @default.
• W2006802243 cites W1979912064 @default.
• W2006802243 cites W1984196084 @default.
• W2006802243 cites W1987341100 @default.
• W2006802243 cites W1988986946 @default.
• W2006802243 cites W1989972829 @default.
• W2006802243 cites W1991991142 @default.
• W2006802243 cites W1996480247 @default.
• W2006802243 cites W1996837502 @default.
• W2006802243 cites W1997426613 @default.
• W2006802243 cites W2004266498 @default.
• W2006802243 cites W2021212968 @default.
• W2006802243 cites W2025302671 @default.
• W2006802243 cites W2029532449 @default.
• W2006802243 cites W2030011352 @default.
• W2006802243 cites W2034933548 @default.
• W2006802243 cites W2034969383 @default.
• W2006802243 cites W2040897211 @default.
• W2006802243 cites W2042148434 @default.
• W2006802243 cites W2043305034 @default.
• W2006802243 cites W2051495044 @default.
• W2006802243 cites W2051573772 @default.
• W2006802243 cites W2053116497 @default.
• W2006802243 cites W2058419251 @default.
• W2006802243 cites W2064466771 @default.
• W2006802243 cites W2068001868 @default.
• W2006802243 cites W2070417141 @default.
• W2006802243 cites W2074562451 @default.
• W2006802243 cites W2076517751 @default.
• W2006802243 cites W2087445413 @default.
• W2006802243 cites W2088608159 @default.
• W2006802243 cites W2092788481 @default.
• W2006802243 cites W2093076184 @default.
• W2006802243 cites W2095745901 @default.
• W2006802243 cites W2096410114 @default.
• W2006802243 cites W2109980291 @default.
• W2006802243 cites W2110888808 @default.
• W2006802243 cites W2117983251 @default.
• W2006802243 cites W2122437043 @default.
• W2006802243 cites W2125172225 @default.
• W2006802243 cites W2129337589 @default.
• W2006802243 cites W2150999725 @default.
• W2006802243 cites W2155133303 @default.
• W2006802243 cites W2158989452 @default.
• W2006802243 cites W2159838014 @default.
• W2006802243 cites W223894170 @default.
• W2006802243 cites W2395863613 @default.
• W2006802243 cites W4241168058 @default.
• W2006802243 doi "https://doi.org/10.1016/j.bbapap.2005.02.013" @default.
• W2006802243 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16054018" @default.
• W2006802243 hasPublicationYear "2005" @default.
• W2006802243 type Work @default.
• W2006802243 sameAs 2006802243 @default.
• W2006802243 citedByCount "69" @default.
• W2006802243 countsByYear W20068022432012 @default.
• W2006802243 countsByYear W20068022432013 @default.
• W2006802243 countsByYear W20068022432014 @default.
• W2006802243 countsByYear W20068022432015 @default.
• W2006802243 countsByYear W20068022432016 @default.
• W2006802243 countsByYear W20068022432017 @default.
• W2006802243 countsByYear W20068022432018 @default.
• W2006802243 countsByYear W20068022432019 @default.
• W2006802243 countsByYear W20068022432020 @default.
• W2006802243 countsByYear W20068022432021 @default.
• W2006802243 countsByYear W20068022432022 @default.
• W2006802243 countsByYear W20068022432023 @default.
• W2006802243 crossrefType "journal-article" @default.
• W2006802243 hasAuthorship W2006802243A5002819177 @default.
• W2006802243 hasAuthorship W2006802243A5023317571 @default.
• W2006802243 hasAuthorship W2006802243A5091908663 @default.
• W2006802243 hasConcept C104826730 @default.
• W2006802243 hasConcept C126322002 @default.
• W2006802243 hasConcept C134018914 @default.
• W2006802243 hasConcept C169760540 @default.
• W2006802243 hasConcept C170493617 @default.
• W2006802243 hasConcept C181199279 @default.
• W2006802243 hasConcept C2776775109 @default.
• W2006802243 hasConcept C2779134260 @default.
• W2006802243 hasConcept C2780942790 @default.
• W2006802243 hasConcept C2781161787 @default.
• W2006802243 hasConcept C502032728 @default.
• W2006802243 hasConcept C55493867 @default.

• next