Identification of the Multicatalytic Enzyme as a Possible γ-Secretase for the Amyloid Precursor Protein

D. I. Mundy

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

One of the main components of the senile plaques in brain tissue from patients with Alzheimer′s disease is the β-amyloid peptide. This peptide is proteolytically cleaved from the amyloid precursor protein by the action of at least two proteases, a β-secretase which generates the N-terminus and a γ-secretase which generates the C-terminus. Neither of these proteases have been identified. To identify proteases that are candidates for the γ-secretase we synthesized a small fluorescent peptide substrate containing the amino acids comprising the C-terminus of the longest β-amyloid peptide identified. This substrate is hydrolyzed by a single activity in homogenates from both cells and brain tissue and we have demonstrated that this activity is the multicatalytic enzyme or proteasome. Furthermore, using specific inhibitors, we have demonstrated that the fluorescent substrate is hydrolyzed by the chymotrypsin-like activity of the multicatalytic enzyme.

Original languageEnglish (US)
Pages (from-to)333-341
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume204
Issue number1
DOIs
StatePublished - Oct 15 1994

Fingerprint

Amyloid Precursor Protein Secretases
Peptides
Peptide Hydrolases
Enzymes
Amyloid
Brain
Substrates
Tissue
Amyloid beta-Protein Precursor
Amyloid Plaques
Chymotrypsin
Proteasome Endopeptidase Complex
Alzheimer Disease
Amino Acids

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry

Cite this

Identification of the Multicatalytic Enzyme as a Possible γ-Secretase for the Amyloid Precursor Protein. / Mundy, D. I.

In: Biochemical and Biophysical Research Communications, Vol. 204, No. 1, 15.10.1994, p. 333-341.

Research output: Contribution to journalArticle

@article{f5a87ceb2f05461c9f82769e5a89c9cf,
title = "Identification of the Multicatalytic Enzyme as a Possible γ-Secretase for the Amyloid Precursor Protein",
abstract = "One of the main components of the senile plaques in brain tissue from patients with Alzheimer′s disease is the β-amyloid peptide. This peptide is proteolytically cleaved from the amyloid precursor protein by the action of at least two proteases, a β-secretase which generates the N-terminus and a γ-secretase which generates the C-terminus. Neither of these proteases have been identified. To identify proteases that are candidates for the γ-secretase we synthesized a small fluorescent peptide substrate containing the amino acids comprising the C-terminus of the longest β-amyloid peptide identified. This substrate is hydrolyzed by a single activity in homogenates from both cells and brain tissue and we have demonstrated that this activity is the multicatalytic enzyme or proteasome. Furthermore, using specific inhibitors, we have demonstrated that the fluorescent substrate is hydrolyzed by the chymotrypsin-like activity of the multicatalytic enzyme.",
author = "Mundy, {D. I.}",
year = "1994",
month = "10",
day = "15",
doi = "10.1006/bbrc.1994.2464",
language = "English (US)",
volume = "204",
pages = "333--341",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Identification of the Multicatalytic Enzyme as a Possible γ-Secretase for the Amyloid Precursor Protein

AU - Mundy, D. I.

PY - 1994/10/15

Y1 - 1994/10/15

N2 - One of the main components of the senile plaques in brain tissue from patients with Alzheimer′s disease is the β-amyloid peptide. This peptide is proteolytically cleaved from the amyloid precursor protein by the action of at least two proteases, a β-secretase which generates the N-terminus and a γ-secretase which generates the C-terminus. Neither of these proteases have been identified. To identify proteases that are candidates for the γ-secretase we synthesized a small fluorescent peptide substrate containing the amino acids comprising the C-terminus of the longest β-amyloid peptide identified. This substrate is hydrolyzed by a single activity in homogenates from both cells and brain tissue and we have demonstrated that this activity is the multicatalytic enzyme or proteasome. Furthermore, using specific inhibitors, we have demonstrated that the fluorescent substrate is hydrolyzed by the chymotrypsin-like activity of the multicatalytic enzyme.

AB - One of the main components of the senile plaques in brain tissue from patients with Alzheimer′s disease is the β-amyloid peptide. This peptide is proteolytically cleaved from the amyloid precursor protein by the action of at least two proteases, a β-secretase which generates the N-terminus and a γ-secretase which generates the C-terminus. Neither of these proteases have been identified. To identify proteases that are candidates for the γ-secretase we synthesized a small fluorescent peptide substrate containing the amino acids comprising the C-terminus of the longest β-amyloid peptide identified. This substrate is hydrolyzed by a single activity in homogenates from both cells and brain tissue and we have demonstrated that this activity is the multicatalytic enzyme or proteasome. Furthermore, using specific inhibitors, we have demonstrated that the fluorescent substrate is hydrolyzed by the chymotrypsin-like activity of the multicatalytic enzyme.

UR - http://www.scopus.com/inward/record.url?scp=0028113253&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028113253&partnerID=8YFLogxK

U2 - 10.1006/bbrc.1994.2464

DO - 10.1006/bbrc.1994.2464

M3 - Article

C2 - 7945379

AN - SCOPUS:0028113253

VL - 204

SP - 333

EP - 341

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 1

ER -