Matches in SemOpenAlex for { <https://semopenalex.org/work/W2022243743> ?p ?o ?g. }
- W2022243743 abstract "Presenilin-1 (PS1) and presenilin-2 (PS2) are transmembrane proteins widely expressed in the central nervous system, which function as the catalytic subunits of γ-secretase, the enzyme that releases amyloid-β protein (Aβ) from ectodomain cleaved amyloid precursor protein (APP) by intramembrane proteolysis. Mutations in PS1, PS2, and Aβ protein precursor are involved in the etiology of familial Alzheimer’s disease (FAD), while the cause of the sporadic form of AD (SAD) is still not known. However, since similar neuropathological changes have been observed in both FAD and SAD, a common pathway in the etiology of the disease has been suggested. Given that age-related deranged Ca 2+ regulation has been hypothesized to play a role in SAD pathogenesis via PS gene regulation and γ-secretase activity, we studied the in vitro regulation of PS1 and PS2 in the human neuron-like SK-N-BE cell line treated with the specific endoplasmic reticulum (ER) calcium ATPase inhibitor Thapsigargin (THG), to introduce intracellular Ca 2+ perturbations and mimic the altered Ca 2+ homeostasis observed in AD. Our results showed a consistent and significant down-regulation of PS2, while PS1 appeared to be unmodulated. These events were accompanied by oxidative stress and a number of morphological alterations suggestive of the induction of apoptotic machinery. The administration of the antioxidant N-acetylcysteine (NAC) did not revert the THG-induced effects reported, while treatment with the Ca 2+ -independent ER stressor Brefeldin A did not modulate basal PS1 and PS2 expression. Collectively, these results suggest that Ca 2+ fluctuation rather than ER stress and/or oxidative imbalance seems to play an essential role in PS2 regulation and confirm that, despite their strong homology, PS1 and PS2 could play different roles in AD." @default.
- W2022243743 created "2016-06-24" @default.
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- W2022243743 date "2013-12-20" @default.
- W2022243743 modified "2023-09-23" @default.
- W2022243743 title "Thapsigargin affects presenilin-2 but not presenilin-1 regulation in SK-N-BE cells" @default.
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- W2022243743 doi "https://doi.org/10.1177/1535370213514317" @default.
- W2022243743 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24363250" @default.
- W2022243743 hasPublicationYear "2013" @default.
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