The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential.
The beta-amyloid (Abeta) peptide is the major constituent of amyloid plaques in Alzheimer's disease (AD) brain and is likely to play a central role in the pathogenesis of this devastating neurodegenerative disorder. The beta-secretase, beta-site amyloid precursor protein cleaving enzyme (BACE1; also called Asp2, memapsin 2), is the enzyme responsible for initiating Abeta generation. Thus, BACE is a prime drug target for the therapeutic inhibition of Abeta production in AD. Since its discovery 10 years ago, much has been learned about BACE. This review summarizes BACE properties, describes BACE translation dysregulation in AD, and discusses BACE physiological functions in sodium current, synaptic transmission, myelination, and schizophrenia. The therapeutic potential of BACE will also be considered. This is a summary of topics covered at a symposium held at the 39th annual meeting of the Society for Neuroscience and is not meant to be a comprehensive review of BACE.
Vassar
Robert
R
Department of Cell and Molecular Biology, Northwestern University, Chicago, Illinois 60611, USA. r-vassar@northwestern.edu
Kovacs
Dora M
DM
Yan
Riqiang
R
Wong
Philip C
PC
D000544:Alzheimer Disease / Q000201:enzymology* / Q000628:therapy*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011480:Protease Inhibitors / Q000378:metabolism / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human