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Identification of a putative amyloid A4‐generating enzyme as a prolyl endopeptidase
Author(s) -
Ishiura Shoichi,
Tsukahara Toshifumi,
Tabira Takeshi,
Shimizu Teruo,
Arahata Kiichi,
Sugita Hideo
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)80084-v
Subject(s) - peptide , p3 peptide , endopeptidase , amyloid precursor protein , biochemistry , neprilysin , chemistry , amyloid (mycology) , prolyl endopeptidase , enzyme , alzheimer's disease , disease , medicine , pathology , inorganic chemistry
The A4 amyloid peptide is deposited in Alzheimer's disease inside neurons as neurofibrillary tangles or extracellularly as vascular amyloid. The A4 peptide is cleaved off by an unidentified proteinase from a larger precursor protein (APP), which resembles a cell surface receptor. The proteinase, which cleaves off the membrane‐spanning domain of APP, may be important in amyloid formation. To evaluate this, a model peptide substrate, succinyl‐ isoleucyl‐alanine‐methylcoumarinamide, which is homologous to the C‐terminal portion of A4 peptide, was synthesized to screen the putative A4‐generating proteinase. On chromatographie purification, it was found that two proteinases are involved in the hydrolysis of the peptide, the major one being identified as a prolyl endopeptidase. This evidence may facilitate elucidation of the mechanism of amyloid deposition in Alzheimer's disease.