NR AECH

AU Forloni,G.

TI Neurotoxicity of beta-amyloid and prion peptides

QU Current Opinion in Neurology 1996 Dec; 9(6): 492-500

PT journal article; review; review, tutorial

AB Neuropathological observations, supported by genetic and biochemical studies, indicate the central role of amyloid-beta protein deposits in the pathogenesis of Alzheimer's disease. In prion-related encephalopathies also, an altered form of prion protein forms amyloid fibrils and accumulates in the brain. In both conditions the amyloid deposition is accompanied by nerve cell loss, the pathogenesis and molecular basis of which are not understood. Synthetic peptides homologous to amyloid-beta protein and its fragments and to prion protein fragments are utilized to investigate the mechanisms of cerebral deposit formation and the role played by these proteins in Alzheimer's disease and prion-related encephalopathies, respectively. Amyloid-beta protein peptides have been shown to be neurotoxic and amyloidogenic under experimental conditions and numerous studies have been performed to clarify the mechanism of neuronal death induced by exposure to these peptides. Peptides homologous to the fragment 106-126 of prion protein, an integral part of all abnormal prion protein isoforms that accumulate in the brain of patients with prion-related encephalopathies, are neurotoxic, fibrillogenic, and have a secondary structure largely composed of beta-sheet and proteinase-resistant properties.

ZR 111

MH Alzheimer Disease/*genetics/pathology; Amyloid beta-Protein/*genetics; Brain/pathology; Human; Nerve Degeneration/*genetics; Neurofibrillary Tangles/genetics/pathology; Peptide Fragments/genetics; Prion Diseases/*genetics/pathology; Prions/*genetics; Support, Non-U.S. Gov't

AD Biology of Neurodegenerative Disorders Laboratory, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.

SP englisch

PO USA

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