Arginine specific endopeptidases modify the aggregation properties of a synthetic peptide derived from Alzheimer

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T Honda1, C A Marotta

  • 1Molecular Neurobiology Laboratory, McLean Hospital, Belmont, Massachusetts.

Neurochemical Research
|April 1, 1992
PubMed

Insights

Alzheimer disease amyloid beta/A4 peptide aggregates were degraded by most proteases, but arginine-specific proteases created a larger, more complex aggregate. This suggests a potential mechanism for Alzheimer

Area of Science:

  • Neuroscience
  • Biochemistry
  • Molecular Biology

Background:

  • Alzheimer disease is characterized by amyloid beta/A4 peptide aggregation.
  • The aggregation process and its modulation by enzymes are not fully understood.

Purpose of the Study:

  • To investigate the proteolytic processing of aggregated Alzheimer disease amyloid beta/A4 peptide.
  • To determine the effect of arginine-specific proteases on amyloid aggregate structure.

Main Methods:

  • Synthetic beta/A4(1-28) peptide was aggregated.
  • Aggregates were subjected to digestion by various proteases, including arginine-specific ones.
  • Digestion products were analyzed using SDS/urea polyacrylamide gel electrophoresis.

Main Results:

  • Most proteases degraded the amyloid aggregate into smaller peptides.
  • Arginine-specific proteases (endopeptidase Arg-C, nerve growth factor gamma subunit, clostripain) generated a higher molecular weight aggregate (16 kDa) without smaller degradation products.
  • This new aggregate contained intact beta/A4(1-28) and partially degraded fragments beta/A4(1-5) and beta/A4(6-28).

Conclusions:

  • Arginine-specific proteases can nick aggregated beta/A4(1-28) and form more complex, higher molecular weight aggregates.
  • This proteolytic mechanism may contribute to the formation of insoluble senile plaque core protein in Alzheimer disease brains.

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