Epsilon-secretase: reduction of amyloid precursor protein epsilon-site cleavage in Alzheimer's disease.
The accumulation and deposition of fibrillar Abeta is thought the primary cause of Alzheimer's disease (AD). Abeta is generated by sequential proteolytic processing involving beta- and gamma-secretase on Amyloid beta protein precursor (APP). Recently, gamma-secretase was shown to cleave near the cytoplasmic membrane boundary of APP, called epsilon-site cleavage, as well as in the middle of the membrane domain, called gamma-site cleavage. Recent findings indicate that gamma- and epsilon-site cleavage are regulated independently. In this review, the reduction of epsilon-site cleavage in AD and the importance of epsilon-site cleavage are discussed.
Kametani
Fuyuki
F
Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan. kametani@prit.go.jp
D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans
D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases