Identification of a putative amyloid A4‐generating enzyme as a prolyl endopeptidase

FEBS Letters

Sugita, Hideo¹  Tabira, Takeshi¹  Arahata, Kiichi¹  Tsukahara, Toshifumi¹  Ishiura, Shoichi¹  Shimizu, Teruo¹ 

[1] National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187, Japan

关键词: Amyloid;    A4 peptide;    Prolyl endopeptidase;    Alzheimer's disease;    (Rat brain);   

DOI  :  10.1016/0014-5793(90)80084-V

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown