Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912542521> ?p ?o ?g. }
- W2912542521 abstract "Allele-specific distinctions in the human ApolipoproteinE (ApoE) locus represent the best characterized genetic predictor of Alzheimer's disease (AD) risk. Expression of isoform ApoEε2 is associated with reduced risk, while ApoEε3 is neutral and ApoEε4 carriers exhibit increased susceptibility. Using Caenorhabditis elegans, we generated a novel suite of humanized transgenic nematodes to facilitate neuronal modeling of amyloid-beta peptide (Aβ) co-expression in the context of distinct human ApoE alleles. We found that co-expression of human ApoEε2 with Aβ attenuated Aβ-induced neurodegeneration, while expression of the ApoEε4 allele had no effect on neurodegeneration, indicating a loss of neuroprotective capacity. Notably, the ApoEε3 allele displayed an intermediate phenotype; it was not neuroprotective in young adults but attenuated neurodegeneration in older animals. There was no functional impact from the three ApoE isoforms in the absence of Aβ co-expression. Pharmacological treatment that examined neuroprotective effects of ApoE alleles on calcium homeostasis showed allele-specific responses to changes in ER-associated calcium dynamics in the Aβ background. Additionally, Aβ suppressed survival, an effect that was rescued by ApoEε2 and ApoEε3, but not ApoEε4. Expression of the ApoE alleles in neurons, independent of Aβ, exerted no impact on survival. Taken together, these results illustrate that C. elegans provides a powerful in vivo platform with which to explore how AD-associated neuronal pathways are modulated by distinct ApoE gene products in the context of Aβ-associated neurotoxicity. The significance of both ApoE and Aβ to AD highlights the utility of this new pre-clinical model as a means to dissect their functional interrelationship." @default.
- W2912542521 created "2019-02-21" @default.
- W2912542521 creator A5013184672 @default.
- W2912542521 creator A5015274628 @default.
- W2912542521 creator A5021793424 @default.
- W2912542521 creator A5033267154 @default.
- W2912542521 creator A5039793742 @default.
- W2912542521 creator A5045083717 @default.
- W2912542521 creator A5061839452 @default.
- W2912542521 creator A5083475944 @default.
- W2912542521 date "2019-01-01" @default.
- W2912542521 modified "2023-09-26" @default.
- W2912542521 title "ApoE-associated modulation of neuroprotection from Aβ-mediated neurodegeneration in transgenic <i>Caenorhabditis elegans</i>" @default.
- W2912542521 cites W1516940938 @default.
- W2912542521 cites W1558528060 @default.
- W2912542521 cites W156047692 @default.
- W2912542521 cites W1619158228 @default.
- W2912542521 cites W1669771493 @default.
- W2912542521 cites W1904905451 @default.
- W2912542521 cites W1927567505 @default.
- W2912542521 cites W1944127002 @default.
- W2912542521 cites W1966083586 @default.
- W2912542521 cites W1966831629 @default.
- W2912542521 cites W1967016606 @default.
- W2912542521 cites W1968721593 @default.
- W2912542521 cites W1970779072 @default.
- W2912542521 cites W1973951644 @default.
- W2912542521 cites W1974878596 @default.
- W2912542521 cites W1975595547 @default.
- W2912542521 cites W1976531450 @default.
- W2912542521 cites W1978451224 @default.
- W2912542521 cites W1980342220 @default.
- W2912542521 cites W1980750700 @default.
- W2912542521 cites W1985042306 @default.
- W2912542521 cites W1985927048 @default.
- W2912542521 cites W1987832889 @default.
- W2912542521 cites W1992869587 @default.
- W2912542521 cites W1994305081 @default.
- W2912542521 cites W1998219375 @default.
- W2912542521 cites W1998470289 @default.
- W2912542521 cites W2002181764 @default.
- W2912542521 cites W2002439304 @default.
- W2912542521 cites W2003439867 @default.
- W2912542521 cites W2005036104 @default.
- W2912542521 cites W2005727437 @default.
- W2912542521 cites W2006534012 @default.
- W2912542521 cites W2008290466 @default.
- W2912542521 cites W2009741382 @default.
- W2912542521 cites W2016443299 @default.
- W2912542521 cites W2018351107 @default.
- W2912542521 cites W2021547032 @default.
- W2912542521 cites W2023605278 @default.
- W2912542521 cites W2023974334 @default.
- W2912542521 cites W2029616852 @default.
- W2912542521 cites W2030508474 @default.
- W2912542521 cites W2031365272 @default.
- W2912542521 cites W2034213169 @default.
- W2912542521 cites W2036362108 @default.
- W2912542521 cites W2038976773 @default.
- W2912542521 cites W2039848901 @default.
- W2912542521 cites W2040522662 @default.
- W2912542521 cites W2042421739 @default.
- W2912542521 cites W2046989794 @default.
- W2912542521 cites W2051629075 @default.
- W2912542521 cites W2052722557 @default.
- W2912542521 cites W2058615553 @default.
- W2912542521 cites W2061756062 @default.
- W2912542521 cites W2064329597 @default.
- W2912542521 cites W2069863984 @default.
- W2912542521 cites W2071993554 @default.
- W2912542521 cites W2075139515 @default.
- W2912542521 cites W2080094749 @default.
- W2912542521 cites W2085320551 @default.
- W2912542521 cites W2088685374 @default.
- W2912542521 cites W2089187276 @default.
- W2912542521 cites W2090271811 @default.
- W2912542521 cites W2093561921 @default.
- W2912542521 cites W2097039472 @default.
- W2912542521 cites W2098104802 @default.
- W2912542521 cites W2100977491 @default.
- W2912542521 cites W2104177210 @default.
- W2912542521 cites W2109188407 @default.
- W2912542521 cites W2109502717 @default.
- W2912542521 cites W2111723622 @default.
- W2912542521 cites W2114091917 @default.
- W2912542521 cites W2117875646 @default.
- W2912542521 cites W2118417727 @default.
- W2912542521 cites W2124165977 @default.
- W2912542521 cites W2130044053 @default.
- W2912542521 cites W2130144581 @default.
- W2912542521 cites W2130622073 @default.
- W2912542521 cites W2132957118 @default.
- W2912542521 cites W2138340537 @default.
- W2912542521 cites W2138992810 @default.
- W2912542521 cites W2140718540 @default.
- W2912542521 cites W2143802939 @default.
- W2912542521 cites W2145138002 @default.
- W2912542521 cites W2145808773 @default.
- W2912542521 cites W2150609468 @default.
- W2912542521 cites W2152430821 @default.