In vitro Generation of Amyloid βA4 Peptide from Amyloid Protein Precursor Through Nonspecific Proteolysis


	Pakistan Journal of Biological Sciences
	Year: 2001 \| Volume: 4 \| Issue: 3 \| Page No.: 289-292 DOI: 10.3923/pjbs.2001.289.292

In vitro Generation of Amyloid βA4 Peptide from Amyloid Protein Precursor Through Nonspecific Proteolysis

Golam Sadik, Kazuya Takeda, Hiroyuki Kaji , Masato Taoka and Tomotaka Shinoda

Abstract: Amyloid βA4 peptide, the principal constituents of the senile plaques in Alzheimer`s disease (AD) originates from proteolysis of a larger protein precursor (APP). Several lines of evidence suggest that this peptide may be generated from aggregated precursor through nonspecific proteolysis. In this work, we used a sensitive in vitro method of detection to investigate the role of nonspecific proteases in the processing of a 100-amino acid C-terminal fragment (C100) inclusive of βA4 and cytoplasmic domain of APP. We demonstrate first that C100 forms high molecular weight aggregates in vitro as determined by size exclusion chromatography. Digestion of aggregated C100 with the nonspecific enzyme, proteinase K resulted in cleavage at the amyloidogenic -secretase sites. This occurred at Ala 42-Val 43 generating βA4 12-42 & βA4 16-42 amyloid peptides. The enzyme cleaved most of the peptide bonds of the cytoplasmic domain and the upstream of βA4 domain of the substrate. The result suggests that both the N- and C-terminus βA4 can be generated by nonspecific proteases, acting on a aggregated substrate and support the notion that the βA4 can be formed in organelles containing proteases capable of cleaving most peptide bonds.

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How to cite this article:

Golam Sadik, Kazuya Takeda, Hiroyuki Kaji , Masato Taoka and Tomotaka Shinoda , 2001. In vitro Generation of Amyloid βA4 Peptide from Amyloid Protein Precursor Through Nonspecific Proteolysis. Pakistan Journal of Biological Sciences, 4: 289-292.

DOI: 10.3923/pjbs.2001.289.292

URL: https://scialert.net/abstract/?doi=pjbs.2001.289.292

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