FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3155495220> ?p ?o ?g. }

• W3155495220 endingPage "839" @default.
• W3155495220 startingPage "823" @default.
• W3155495220 abstract "One of the main components of senile plaques in Alzheimer's disease (AD)-affected brain is the Aβ peptide species harboring a pyroglutamate at position three pE3-Aβ. Several studies indicated that pE3-Aβ is toxic, prone to aggregation and serves as a seed of Aβ aggregation. The cyclisation of the glutamate residue is produced by glutaminyl cyclase, the pharmacological and genetic reductions of which significantly alleviate AD-related anatomical lesions and cognitive defects in mice models. The cyclisation of the glutamate in position 3 requires prior removal of the Aβ N-terminal aspartyl residue to allow subsequent biotransformation. The enzyme responsible for this rate-limiting catalytic step and its relevance as a putative trigger of AD pathology remained yet to be established. Here, we identify aminopeptidase A as the main exopeptidase involved in the N-terminal truncation of Aβ and document its key contribution to AD-related anatomical and behavioral defects. First, we show by mass spectrometry that human recombinant aminopeptidase A (APA) truncates synthetic Aβ1-40 to yield Aβ2-40. We demonstrate that the pharmacological blockade of APA with its selective inhibitor RB150 restores the density of mature spines and significantly reduced filopodia-like processes in hippocampal organotypic slices cultures virally transduced with the Swedish mutated Aβ-precursor protein (βAPP). Pharmacological reduction of APA activity and lowering of its expression by shRNA affect pE3-42Aβ- and Aβ1-42-positive plaques and expressions in 3xTg-AD mice brains. Further, we show that both APA inhibitors and shRNA partly alleviate learning and memory deficits observed in 3xTg-AD mice. Importantly, we demonstrate that, concomitantly to the occurrence of pE3-42Aβ-positive plaques, APA activity is augmented at early Braak stages in sporadic AD brains. Overall, our data indicate that APA is a key enzyme involved in Aβ N-terminal truncation and suggest the potential benefit of targeting this proteolytic activity to interfere with AD pathology." @default.
• W3155495220 created "2021-04-26" @default.
• W3155495220 creator A5007181072 @default.
• W3155495220 creator A5008345508 @default.
• W3155495220 creator A5011145148 @default.
• W3155495220 creator A5025997920 @default.
• W3155495220 creator A5030267777 @default.
• W3155495220 creator A5032132304 @default.
• W3155495220 creator A5054101486 @default.
• W3155495220 creator A5083569231 @default.
• W3155495220 creator A5086409965 @default.
• W3155495220 date "2021-04-21" @default.
• W3155495220 modified "2023-10-16" @default.
• W3155495220 title "Aminopeptidase A contributes to biochemical, anatomical and cognitive defects in Alzheimer’s disease (AD) mouse model and is increased at early stage in sporadic AD brain" @default.
• W3155495220 cites W1520627922 @default.
• W3155495220 cites W1552912270 @default.
• W3155495220 cites W1564371178 @default.
• W3155495220 cites W1577922439 @default.
• W3155495220 cites W1582664727 @default.
• W3155495220 cites W1779570864 @default.
• W3155495220 cites W1891861366 @default.
• W3155495220 cites W189551846 @default.
• W3155495220 cites W1964747897 @default.
• W3155495220 cites W1966014719 @default.
• W3155495220 cites W1967464880 @default.
• W3155495220 cites W1969810313 @default.
• W3155495220 cites W1974145718 @default.
• W3155495220 cites W1980749733 @default.
• W3155495220 cites W1990632702 @default.
• W3155495220 cites W1991435932 @default.
• W3155495220 cites W1995604544 @default.
• W3155495220 cites W2007389732 @default.
• W3155495220 cites W2017898906 @default.
• W3155495220 cites W2028405984 @default.
• W3155495220 cites W2028578297 @default.
• W3155495220 cites W2032958786 @default.
• W3155495220 cites W2034664857 @default.
• W3155495220 cites W2039239447 @default.
• W3155495220 cites W2054238450 @default.
• W3155495220 cites W2061123524 @default.
• W3155495220 cites W2070448139 @default.
• W3155495220 cites W2071310220 @default.
• W3155495220 cites W2080797130 @default.
• W3155495220 cites W2087103161 @default.
• W3155495220 cites W2088233313 @default.
• W3155495220 cites W2090150925 @default.
• W3155495220 cites W2100791245 @default.
• W3155495220 cites W2103440561 @default.
• W3155495220 cites W2108249261 @default.
• W3155495220 cites W2124147311 @default.
• W3155495220 cites W2139375718 @default.
• W3155495220 cites W2150599338 @default.
• W3155495220 cites W2162124438 @default.
• W3155495220 cites W2162798214 @default.
• W3155495220 cites W2231709936 @default.
• W3155495220 cites W2332891257 @default.
• W3155495220 cites W2344407798 @default.
• W3155495220 cites W2399749275 @default.
• W3155495220 cites W2523602889 @default.
• W3155495220 cites W2607046971 @default.
• W3155495220 cites W2610837589 @default.
• W3155495220 cites W2611118767 @default.
• W3155495220 cites W2752326209 @default.
• W3155495220 cites W2883126887 @default.
• W3155495220 cites W2888552223 @default.
• W3155495220 cites W2889621218 @default.
• W3155495220 cites W2913909521 @default.
• W3155495220 cites W2924812437 @default.
• W3155495220 cites W2965717703 @default.
• W3155495220 cites W2972466067 @default.
• W3155495220 cites W2991435795 @default.
• W3155495220 cites W2995252331 @default.
• W3155495220 cites W3004905553 @default.
• W3155495220 cites W3092964313 @default.
• W3155495220 cites W380069984 @default.
• W3155495220 doi "https://doi.org/10.1007/s00401-021-02308-0" @default.
• W3155495220 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8113186" @default.
• W3155495220 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33881611" @default.
• W3155495220 hasPublicationYear "2021" @default.
• W3155495220 type Work @default.
• W3155495220 sameAs 3155495220 @default.
• W3155495220 citedByCount "14" @default.
• W3155495220 countsByYear W31554952202021 @default.
• W3155495220 countsByYear W31554952202022 @default.
• W3155495220 countsByYear W31554952202023 @default.
• W3155495220 crossrefType "journal-article" @default.
• W3155495220 hasAuthorship W3155495220A5007181072 @default.
• W3155495220 hasAuthorship W3155495220A5008345508 @default.
• W3155495220 hasAuthorship W3155495220A5011145148 @default.
• W3155495220 hasAuthorship W3155495220A5025997920 @default.
• W3155495220 hasAuthorship W3155495220A5030267777 @default.
• W3155495220 hasAuthorship W3155495220A5032132304 @default.
• W3155495220 hasAuthorship W3155495220A5054101486 @default.
• W3155495220 hasAuthorship W3155495220A5083569231 @default.
• W3155495220 hasAuthorship W3155495220A5086409965 @default.
• W3155495220 hasBestOaLocation W31554952201 @default.
• W3155495220 hasConcept C148762608 @default.
• W3155495220 hasConcept C169760540 @default.

• next