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Neurotoxicity of Human Amylin in Rat Primary Hippocampal Cultures: Similarity to Alzheimer's Disease Amyloid‐ β Neurotoxicity
Author(s) -
May Patrick C.,
Boggs Leonard N.,
Fuson Kimberly S.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb07480.x
Subject(s) - amylin , neurotoxicity , peptide , amyloid (mycology) , hippocampal formation , biochemistry , amyloid beta , alzheimer's disease , chemistry , neurodegeneration , biology , endocrinology , medicine , toxicity , disease , insulin , inorganic chemistry , islet
Amylin, a 37‐amino‐acid amyloidogenic peptide, bears biophysical similarities to the amyloid‐ β peptide (A β ) deposited in Alzheimer's disease. Using embryonic rat hippocampal cultures we tested whether amylin induces neurotoxicity similar to that previously observed with A β (1–40). Treatment with human amylin (1–37) resulted in prominent toxicity as assessed by phasecontrast microscopy and quantification of lactate dehydrogenase in the medium. Amylin‐induced neurotoxicity was morphologically similar to that induced by A β (1–40). In contrast, the nonamyloidogenic rat amylin showed negligible neurotoxicity despite having 95% sequence similarity to human amylin. Only full‐length human amylin was toxic; various amylin peptide fragments including amino acid residues 20–29 were nontoxic at similar concentrations. These studies suggest that unrelated amyloidogenic peptides like human amylin and A β can adopt a similar neurotoxic conformation in vitro. Similar conformation‐dependent neurotoxicity may drive the prominent neurite degeneration around compacted but not diffuse deposits of A β in Alzheimer's disease.