Neurotoxicity of human amylin in rat primary hippocampal cultures: similarity to Alzheimer's disease amyloid-beta neurotoxicity

J Neurochem. 1993 Dec;61(6):2330-3. doi: 10.1111/j.1471-4159.1993.tb07480.x.

Abstract

Amylin, a 37-amino-acid amyloidogenic peptide, bears biophysical similarities to the amyloid-beta peptide (A beta) deposited in Alzheimer's disease. Using embryonic rat hippocampal cultures we tested whether amylin induces neurotoxicity similar to that previously observed with A beta(1-40). Treatment with human amylin(1-37) resulted in prominent toxicity as assessed by phase-contrast microscopy and quantification of lactate dehydrogenase in the medium. Amylin-induced neurotoxicity was morphologically similar to that induced by A beta(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 beta 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 beta in Alzheimer's disease.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Amyloid / toxicity*
  • Amyloid beta-Peptides / toxicity*
  • Analysis of Variance
  • Animals
  • Cells, Cultured
  • Hippocampus / drug effects*
  • Humans
  • Islet Amyloid Polypeptide
  • L-Lactate Dehydrogenase / analysis
  • Molecular Sequence Data
  • Nerve Degeneration / drug effects*
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurotoxins / toxicity*
  • Rats
  • Sequence Homology, Amino Acid

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Islet Amyloid Polypeptide
  • Neurotoxins
  • L-Lactate Dehydrogenase