Evidence for D-aspartyl-β-amyloid secretase activity in human brain

John M. Lee, Leonardo Petrucelli, George Fisher, Sona Ramdath, James Castillo, M. Maddalena Di Fiore, Antimo D'Aniello

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Alzheimer disease (AD) is characterized neuropathologically by the presence of senile plaques that are composed of the amyloid-β protein (Aβ). Aβ is an insoluble extracellular deposit consisting of 39-43 amino acids that is cleaved from a larger precursor amyloid-βprecursor protein (β-APP). It has been shown that Aβ proteins extracted from amyloid cores of neuritic plaques contain isomerized and/or racemized Asp residues. Therefore, we hypothesized that a specific secretase (s) may exist in the human brain that can cleave a β-APP peptide bond containing D-Asp at position 1 of the Aβ protein. In the present study, we report data to support the existence of a putative membrane-bound D-β-secretase that can cleave between L-Met-D-Asp at the 1 position of the Aβ with a pH optimum in the neutral pH range. The specific enzyme activity of soluble extracts from AD samples was 22% higher compared to age-matched controls.

Original languageEnglish (US)
Pages (from-to)125-131
Number of pages7
JournalJournal of Neuropathology and Experimental Neurology
Volume61
Issue number2
DOIs
StatePublished - 2002

Keywords

  • Alzheimer disease
  • Enzyme
  • High-pressure liquid chromatography (HPLC)
  • Protease
  • Secretase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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