MOLECULAR BASIS OF BIOACTIVITY OF THE β-AMYLOID PROTEIN AND INHIBITORS OF ITS NEUROTOXICITY

It is now accepted that excessive deposition of the β-amyloid protein(βA) in specific regions of the brain as a result of either overexpression or abnormal cleavage of βA precursors or acceleration of aggregation of βA molecules in those tissues is prerequisite and most important in induction of Alz...

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Bibliographic Details
Published in:Japanese Journal of Pharmacology 1996, Vol.71 (suppl.1), p.20-20
Main Authors: Tetsuro Mohri, Tsuneo Takadera, Matsumi Yamazaki, Naoki Sakura, Tadashi Hashimoto
Format: Article
Language:Japanese
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Summary:It is now accepted that excessive deposition of the β-amyloid protein(βA) in specific regions of the brain as a result of either overexpression or abnormal cleavage of βA precursors or acceleration of aggregation of βA molecules in those tissues is prerequisite and most important in induction of Alzheimer s disease. The specific antiparallel β-sheet structure of lengths of βA were elucidated to be responsible for its neurotoxic effect on cultured brain neurons. Synthetic peptide fragments of βA such as β25-35 had varying degrees of neurotoxicity in cultured rat fetal hippocampal cells depending on the concentration in medium devoid of serum. The neurotoxicity of the peptide fragments was depressed by addition of bovine serum, cAMP and several kinds of insulinrelated hormones to medium. We have found natural iridoid compounds to be capable of depressing the neurotoxicity of β25-35(40 μM) dose-dependently as determined by release of lactate dehydrogenase from cultured rat hippocampal neurons.
ISSN:0021-5198