Amyloid at the cutting edge: activation of alpha-secretase prevents amyloidogenesis in an Alzheimer disease mouse model.
The amyloid beta-peptide (A beta peptide) is assumed to play a crucial and early role in the pathogenesis of Alzheimer disease. Thus, strategies for a pharmacotherapy aim at reducing A beta peptide generation, which proteolytically derives from the amyloid precursor protein (APP). The main targets so far have been beta- and gamma-secretase, the two proteases that cleave APP at the N- and C-terminus of the A beta peptide and are thus directly responsible for A beta peptide generation. A different strategy, namely the activation of alpha-secretase, has barely been investigated for its therapeutic potential. alpha-Secretase cleaves within the A beta peptide domain and thus precludes A beta peptide generation. Now, new results demonstrate that activation of alpha-secretase indeed reduces A beta peptide generation and toxicity in vivo.
Lichtenthaler
Stefan F
SF
Adolf-Butenandt-Institut, Laboratory for Alzheimer's and Parkinson's Disease Research, Ludwig-Maximilians-Universität, Munich, Germany. Stefan.Lichtenthaler@med.uni-muenchen.de
Haass
Christian
C
D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases; D000686:Amyloidosis / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D051379:Mice
D000682:Amyloid; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse