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Gamma-secretase is a multiprotein complex composed of presenilin (PS), nicastrin (NCT), Aph-1, and Pen-2, and it catalyzes the final proteolytic step in the processing of amyloid precursor protein to generate amyloid-beta. Our previous results showed that tumor necrosis factor-alpha (TNF-alpha) can potently stimulate gamma-secretase activity through a c-Jun(More)
Autophagy is a major protein degradation pathway that is essential for stress-induced and constitutive protein turnover. Accumulated evidence has demonstrated that amyloid-β (Aβ) protein can be generated in autophagic vacuoles, promoting its extracellular deposition in neuritic plaques as the pathological hallmark of Alzheimer’s disease (AD). The molecular(More)
Previous studies have demonstrated that the ERK MAPK acts as a negative regulator of gamma-secretase. Here, we demonstrate that the activation of ERK MAPK pathway by sodium selenite can inhibit endogenous gamma-secretase activity. Consistently, the gamma-secretase-mediated production of amyloid-beta (Abeta) was dramatically attenuated by sodium selenite in(More)
Mammalian p62/sequestosome-1 protein binds to both LC3, the mammalian homologue of yeast Atg8, and polyubiquitinated cargo proteins destined to undergo autophagy-mediated degradation. We previously identified a cargo receptor-binding domain in Atg8 that is essential for its interaction with the cargo receptor Atg19 in selective autophagic processes in(More)
A type of new 1,2,3,4-tetrahydroisoquinoline derivatives was synthesized via concise procedure from commercially available tetrahydroisoquinoline. These derivatives were delicately designed to possess propargyl-related pharmacophores simulated with a monoamine oxidase inhibitor rasagiline. We investigated the effect of these synthetic tetrahydroisoquinoline(More)
Dioxin and dioxin-like compounds are among the most prevalent and toxic environmental pollutants. At present, analytical chemical techniques are considered the gold standard for detection of dioxins. Here, we describe a highly sensitive and cost-effective alternative, based on bioluminescence and bioluminescence resonance energy transfer (BRET). Upon(More)
Proteolytic processing of amyloid precursor protein (APP) C-terminal fragments (CTFs) by γ-secretase underlies the pathogenesis of Alzheimer's disease (AD). An RNA interference screen using APP-CTF [99-residue CTF (C99)]- and Notch-specific γ-secretase interaction assays identified a unique ErbB2-centered signaling network that was predicted to(More)
Mutations in presenilin-1 (PS1) are tightly associated with early-onset familial Alzheimer’s disease (FAD), which is characterized by extracellular amyloid plaques and the accumulation of intracellular Tau. In addition to being the catalytic subunit of γ-secretase, PS1 has been shown to regulate diverse cellular functions independent of its proteolytic(More)
The initial rostrocaudal patterning of the neural tube leads to differential expression of Hox genes that contribute to the specification of motor neuron (MN) subtype identity. Although several 3' Hox mRNAs are expressed in progenitors in a noisy manner, these Hox proteins are not expressed in the progenitors and only become detectable in postmitotic MNs.(More)