FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2805481194> ?p ?o ?g. }

• W2805481194 endingPage "1154" @default.
• W2805481194 startingPage "1129" @default.
• W2805481194 abstract "Macroautophagy/autophagy failure with the accumulation of autophagosomes is an early neuropathological feature of Alzheimer disease (AD) that directly affects amyloid beta (Aβ) metabolism. Although loss of presenilin 1 function has been reported to impair lysosomal function and prevent autophagy flux, the detailed mechanism leading to autophagy dysfunction in AD remains to be elucidated. The resemblance between pathological hallmarks of AD and Niemann-Pick Type C disease, including endosome-lysosome abnormalities and impaired autophagy, suggests cholesterol accumulation as a common link. Using a mouse model of AD (APP-PSEN1-SREBF2 mice), expressing chimeric mouse-human amyloid precursor protein with the familial Alzheimer Swedish mutation (APP695swe) and mutant presenilin 1 (PSEN1-dE9), together with a dominant-positive, truncated and active form of SREBF2/SREBP2 (sterol regulatory element binding factor 2), we demonstrated that high brain cholesterol enhanced autophagosome formation, but disrupted its fusion with endosomal-lysosomal vesicles. The combination of these alterations resulted in impaired degradation of Aβ and endogenous MAPT (microtubule associated protein tau), and stimulated autophagy-dependent Aβ secretion. Exacerbated Aβ-induced oxidative stress in APP-PSEN1-SREBF2 mice, due to cholesterol-mediated depletion of mitochondrial glutathione/mGSH, is critical for autophagy induction. In agreement, in vivo mitochondrial GSH recovery with GSH ethyl ester, inhibited autophagosome synthesis by preventing the oxidative inhibition of ATG4B deconjugation activity exerted by Aβ. Moreover, cholesterol-enrichment within the endosomes-lysosomes modified the levels and membrane distribution of RAB7A and SNAP receptors (SNAREs), which affected its fusogenic ability. Accordingly, in vivo treatment with 2-hydroxypropyl-β-cyclodextrin completely rescued these alterations, making it a potential therapeutic tool for AD." @default.
• W2805481194 created "2018-06-13" @default.
• W2805481194 creator A5011614855 @default.
• W2805481194 creator A5018175469 @default.
• W2805481194 creator A5019266732 @default.
• W2805481194 creator A5028811135 @default.
• W2805481194 creator A5046904851 @default.
• W2805481194 creator A5050631735 @default.
• W2805481194 creator A5058220971 @default.
• W2805481194 creator A5073989246 @default.
• W2805481194 creator A5080139466 @default.
• W2805481194 date "2018-06-04" @default.
• W2805481194 modified "2023-10-18" @default.
• W2805481194 title "Cholesterol impairs autophagy-mediated clearance of amyloid beta while promoting its secretion" @default.
• W2805481194 cites W1562982734 @default.
• W2805481194 cites W1597345104 @default.
• W2805481194 cites W1616122655 @default.
• W2805481194 cites W1883048423 @default.
• W2805481194 cites W1919353 @default.
• W2805481194 cites W196080422 @default.
• W2805481194 cites W1967182910 @default.
• W2805481194 cites W1967502002 @default.
• W2805481194 cites W1971616282 @default.
• W2805481194 cites W1974279922 @default.
• W2805481194 cites W1974790839 @default.
• W2805481194 cites W1983127906 @default.
• W2805481194 cites W1984486531 @default.
• W2805481194 cites W1986198920 @default.
• W2805481194 cites W1989723790 @default.
• W2805481194 cites W1992186496 @default.
• W2805481194 cites W1996617402 @default.
• W2805481194 cites W1997363820 @default.
• W2805481194 cites W1997574987 @default.
• W2805481194 cites W1998019353 @default.
• W2805481194 cites W1999232604 @default.
• W2805481194 cites W2001401503 @default.
• W2805481194 cites W2004127466 @default.
• W2805481194 cites W2009490810 @default.
• W2805481194 cites W2009675282 @default.
• W2805481194 cites W2009734791 @default.
• W2805481194 cites W2011134915 @default.
• W2805481194 cites W2017196579 @default.
• W2805481194 cites W2017274978 @default.
• W2805481194 cites W2018400498 @default.
• W2805481194 cites W2019256890 @default.
• W2805481194 cites W2021121989 @default.
• W2805481194 cites W2022812113 @default.
• W2805481194 cites W2029645812 @default.
• W2805481194 cites W2030641075 @default.
• W2805481194 cites W2031754652 @default.
• W2805481194 cites W2032096651 @default.
• W2805481194 cites W2032687345 @default.
• W2805481194 cites W2034212405 @default.
• W2805481194 cites W2034888251 @default.
• W2805481194 cites W2037653131 @default.
• W2805481194 cites W2039531276 @default.
• W2805481194 cites W2040516491 @default.
• W2805481194 cites W2046054972 @default.
• W2805481194 cites W2046607232 @default.
• W2805481194 cites W2054595666 @default.
• W2805481194 cites W2056262005 @default.
• W2805481194 cites W2057220764 @default.
• W2805481194 cites W2057813271 @default.
• W2805481194 cites W2065408118 @default.
• W2805481194 cites W2069275980 @default.
• W2805481194 cites W2075508190 @default.
• W2805481194 cites W2078583436 @default.
• W2805481194 cites W2079569342 @default.
• W2805481194 cites W2082179247 @default.
• W2805481194 cites W2086477221 @default.
• W2805481194 cites W2086871300 @default.
• W2805481194 cites W2089141103 @default.
• W2805481194 cites W2091017147 @default.
• W2805481194 cites W2092522921 @default.
• W2805481194 cites W2094241924 @default.
• W2805481194 cites W2095421035 @default.
• W2805481194 cites W2095706874 @default.
• W2805481194 cites W2099540110 @default.
• W2805481194 cites W2100134061 @default.
• W2805481194 cites W2100568496 @default.
• W2805481194 cites W2101418591 @default.
• W2805481194 cites W2102776209 @default.
• W2805481194 cites W2103790898 @default.
• W2805481194 cites W2107493006 @default.
• W2805481194 cites W2110054105 @default.
• W2805481194 cites W2112329697 @default.
• W2805481194 cites W2114806766 @default.
• W2805481194 cites W2122573744 @default.
• W2805481194 cites W2128511360 @default.
• W2805481194 cites W2133548029 @default.
• W2805481194 cites W2134458253 @default.
• W2805481194 cites W2135592618 @default.
• W2805481194 cites W2139595374 @default.
• W2805481194 cites W2142943752 @default.
• W2805481194 cites W2143666437 @default.
• W2805481194 cites W2146134542 @default.
• W2805481194 cites W2155858151 @default.
• W2805481194 cites W2157199552 @default.

• next