In search of an enzyme: the beta-secretase of Alzheimer's disease is an aspartic proteinase.
The deposition of beta-amyloid (Abeta) in the brain is a neuropathological feature of Alzheimer's disease. Abeta is cleaved from its precursor protein (APP) by processing at its N and C termini by enzymes known as beta- and gamma-secretases,respectively. The identity of these enzymes has been elusive but the search for the N-terminal secretase might have ended recently with the almost simultaneous publication by five major laboratories claiming a transmembrane aspartic proteinase to be the long sought after beta-secretase. Even at this early stage of its characterization, this aspartic proteinase fulfils many of the key criteria necessary for beta-secretase. The race is now on to develop inhibitors that could prove effective in halting the progression of Alzheimer's disease.
Howlett
D R
DR
The Dept of Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Essex, CM19 5AW, Harlow, UK.
Simmons
D L
DL
Dingwall
C
C
Christie
G
G
D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology*; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001921:Brain / Q000201:enzymology; D010450:Endopeptidases; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D011499:Protein Processing, Post-Translational; D014018:Tissue Distribution
D016564:Amyloid beta-Protein Precursor; D004791:Enzyme Inhibitors; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human