Overexpression of Neprilysin Reduces Alzheimer Amyloid- 42 (A 42)-induced Neuron Loss and Intraneuronal A 42 Deposits but Causes a Reduction in cAMP-responsive Element-binding Protein-mediated Transcription, Age-dependent Axon Pathology, and Premature Death
نویسندگان
چکیده
From the Laboratory of Neurogenetics and Pathobiology, Laboratory of Neurodegenerative Diseases and Gene Discovery, Farber Institute for Neurosciences, Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, and the **Department of Neurobiology and Behavior, State University of New York, Stony Brook, New York 11794
منابع مشابه
Beta-amyloid1-42 gene transfer model exhibits intraneuronal amyloid, gliosis, tau phosphorylation, and neuronal loss.
Alzheimer disease is characterized by extracellular beta-amyloid (Abeta) plaques and intracellular inclusions containing neurofibrillary tangles of phospho-Tau and intraneuronal Abeta associated with neuronal cell death. We generated a novel gene transfer animal model using lentiviral Abeta(1-42) that resulted in intracellular but not extracellular Abeta accumulations in the targeted rat primar...
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Depending upon the stimulus, neuronal cell death can either be triggered from the cell body (soma) or the axon. We investigated the origin of the degeneration signal in amyloid β (Aβ) induced neuronal cell death in cultured in vitro hippocampal neurons. We discovered that Aβ1-42 toxicity-induced axon degeneration precedes cell death in hippocampal neurons. Overexpression of Bcl-xl inhibited bot...
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The mechanism of widespread neuronal death occurring in Alzheimer's disease (AD) remains enigmatic even after extensive investigation during the last two decades. Amyloid beta 42 peptide (Abeta(1-42)) is believed to play a causative role in the development of AD. Here we expressed human Abeta(1-42) and amyloid beta 40 (Abeta(1-40)) in Drosophila neurons. Abeta(1-42) but not Abeta(1-40) causes a...
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Degeneration of locus coeruleus (LC) noradrenergic forebrain projection neurons is an early feature of Alzheimer's disease. The physiological consequences of this phenomenon are unclear, but observations correlating LC neuron loss with increased Alzheimer's disease pathology in LC projection sites suggest that noradrenaline (NA) is neuroprotective. To investigate this hypothesis, we determined ...
متن کاملBrain neprilysin activity and susceptibility to transgene-induced Alzheimer amyloidosis.
Neprilysin (NEP) is a zinc metalloproteinase that degrades enkephalins, endothelins, and the Alzheimer's disease amyloid beta (Abeta) peptides. NEP-deficient mice possess increased levels of brain Abeta(1-40) and Abeta(1-42). The objective of this study was to determine whether tissue NEP specific activity differs according to age and/or across mouse strains, especially those strains predispose...
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