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Amyloid beta-peptide (Abeta) is implicated as the toxic agent in Alzheimer's disease and is the major component of brain amyloid plaques. In vitro, Abeta causes cell death, but the molecular mechanisms are unclear. We analyzed the early signaling mechanisms involved in Abeta toxicity using the SH-SY5Y neuroblastoma cell line. Abeta caused cell death and(More)
Our previous studies revealed that a proximal region of the N-methyl-D-aspartate receptor 1 (NMDAR1) promoter is important for cell-type-specific expression. We have now explored the contributions of several regulatory elements to this specificity. Deletion of the neuron-restrictive silencer element partially relieved the suppression of promoter activity in(More)
Overexpression of the familial Alzheimer's disease gene Presenilin 2 (PS2) in nerve growth factor-differentiated PC12 cells increased apoptosis induced by trophic factor withdrawal or beta-amyloid. Transfection of antisense PS2 conferred protection against apoptosis induced by trophic withdrawal in nerve growth factor-differentiated or amyloid precursor(More)
We have examined the trafficking and metabolism of the beta-amyloid precursor protein (APP), an APP homolog (APLP1), and TrkB in neurons that lack PS1. We report that PS1-deficient neurons fail to secrete Abeta, and that the rate of appearance of soluble APP derivatives in the conditioned medium is increased. Remarkably, carboxyl-terminal fragments (CTFs)(More)
We reported previously that nerve growth factor (NGF) up-regulates activity of the N-methyl-D-aspartate receptor 1 (NR1) promoter. We have explored the pathways and nuclear targets of NGF signaling in regulating the NR1 promoter. PD98059 and wortmannin, but not rapamycin, significantly attenuated NGF-induced transcriptional activity from an NR1(More)
The p3 peptide [amyloid beta-peptide (Abeta) 17-40/42], derived by alpha- and gamma-secretase cleavage of the amyloid precursor protein (APP), is a major constituent of diffuse plaques in Alzheimer's disease and cerebellar pre-amyloid in Down's syndrome. However, the importance of p3 peptide accumulation in Alzheimer's disease and its toxic properties is(More)
Excessive accumulation of amyloid beta-peptide (Abeta) plays an early and critical role in synapse and neuronal loss in Alzheimer's Disease (AD). Increased oxidative stress is one of the mechanisms whereby Abeta induces neuronal death. Given the lessened susceptibility to oxidative stress exhibited by mice lacking p66Shc, we investigated the role of p66Shc(More)
Certain regions of the human aorta are at greater risk for early and more severe atherosclerotic lesions development than others. Cornhill and coworkers (Cornhill FJ et al.: Arteriosclerosis 5:415, 1985) created maps for the probability of developing atherosclerosis defining the high-probability region (HPR) in the dorsal descending thoracic aorta and the(More)
The processing of Alzheimer's amyloid precursor protein was studied by Western blotting during H2O2 induced apoptosis in cultures of human neuroblastoma cells. A new 5.5 kDa fragment putatively containing intact A beta was detected and found to be highly associated with apoptosis. The results suggest a possible vicious cycle involving H2O2, A beta and(More)