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J Clin Invest. 2004 May;113(10):1384-7.

Amyloid at the cutting edge: activation of alpha-secretase prevents amyloidogenesis in an Alzheimer disease mouse model.

Author information

1
Adolf-Butenandt-Institut, Laboratory for Alzheimer's and Parkinson's Disease Research, Ludwig-Maximilians-Universität, Munich, Germany. Stefan.Lichtenthaler@med.uni-muenchen.de

Abstract

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.

PMID:
15146234
PMCID:
PMC406534
DOI:
10.1172/JCI21746
[Indexed for MEDLINE]
Free PMC Article
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