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• W2028013909 endingPage "457" @default.
• W2028013909 startingPage "447" @default.
• W2028013909 abstract "Attention has focussed on the molecular alterations in neurofibrillary tangles (NFT) in Alzheimer's disease (AD) with the presumption that the events leading to the alterations are involved in the neurodegenerative mechanism. Here I propose that some of the manifestations of NFT result from activation of neuroprotective signaling cascades such as those induced by neurotrophic factors. Increasing data implicate free radicals and calcium in the mechanism of neuronal injury (including cytoskeletal pathology) and death in AD. Increased accumulation of beta-amyloid peptide (A beta), reduced energy availability, and increased oxidative processes are among the age-associated changes in AD that appear to be upstream to increases in cellular free radicals and calcium. Neurotrophic factors influence the expression of gene products known to stabilize calcium homeostasis, suppress free radical accumulation, and protect neurons against AD-relevant insults. The events leading to the cytoskeletal alterations in NFT are not clear although some of the alterations can be induced by excitotoxic and metabolic insults. On the other hand, kinases activated by neurotrophic factors may contribute to tau hyperphosphorylation during brain development and in AD. Activities in both degenerative and protective signaling pathways are subject to modification by aging, and by genetic and environmental factors, suggesting that the multiple cytoskeletal alterations in NFT probably result from concurrent activation of both neurodegenerative and neuroprotective cascades." @default.
• W2028013909 created "2016-06-24" @default.
• W2028013909 creator A5083040475 @default.
• W2028013909 date "1995-05-01" @default.
• W2028013909 modified "2023-09-23" @default.
• W2028013909 title "Degenerative and protective signaling mechanisms in the neurofibrillary pathology of AD" @default.
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• W2028013909 doi "https://doi.org/10.1016/0197-4580(94)00182-z" @default.
• W2028013909 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/7566352" @default.
• W2028013909 hasPublicationYear "1995" @default.
• W2028013909 type Work @default.
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