Alzheimer’s Enzyme and Myelination

Abstract

β-secretase activity is crucial in the production of pathological β-amyloid in Alzheimer's disease (AD). However, its role in normal physiology is unclear, especially given the absence of an obvious phenotype in a knockout mouse for BACE1 (beta-site amyloid precursor protein-cleaving enzyme 1). Willem et al . found that BACE1 (but not its close homolog BACE2) is required for neuregulin (NRG)-mediated peripheral nerve myelination. NRG1 was an in vivo substrate of BACE1, and the BACE-1 knockout mouse fully phenocopied hypomyelination observed in NRG1 heterozygous mutant mice. Thus, BACE-1 plays a physiological role during development in myelination. M. Willem, A. N. Garratt, B. Novak, M. Citron, S. Kaufmann, A. Rittger, B. DeStrooper, P. Saftig, C. Birchmeier, C. Haass, Control of peripheral nerve myelination by the β-secretase BACE1. Science 314 , 664-666 (2006). [Abstract] [Full Text] C. Glabe, Avoiding collateral damage in Alzheimer’s disease treatment. Science 314 , 602-603 (2006). [Abstract] [Full Text]