Translational control of BACE1 may go awry in Alzheimer's disease.
Our understanding of the mechanisms whereby BACE1, the aspartyl protease required for the initial cleavage of APP to generate amyloid-beta (Abeta), is regulated in Alzheimer's disease (AD) remains incomplete. In this issue of Neuron, O'Connor and coworkers show how energy deprivation, a potential risk factor in AD, triggers the phosphorylation of the translation initiation factor eIF2alpha to elevate the translation efficiency of a set of stress-related transcripts, including that of BACE1, and increases the level of BACE1, thereby accelerating amyloidogenesis.
Wong
Philip C
PC
Department of Pathology and Neuroscience and the Division of Neuropathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. wong@jhmi.edu
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; 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*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006801:Humans; D014176:Protein Biosynthesis / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D015852:Eukaryotic Initiation Factor-2; C451460:FUN12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human