- Institutionen för anatomi, fysiologi och biokemi, Sveriges lantbruksuniversitet
Johansson, Jan; Peng, S
In Alzheimer's disease the amyloid beta-peptide (A beta) aggregates in brain tissue and arteries. A beta is proteolytically cleaved out from amyloid precursor protein (APP) by different secretases. Recently, the transmembrane protein ITM2B/Bri2, which is expressed in neurons and associated with familial British and Danish dementia, was shown to inhibit APP processing in transfected cells as well as in transgenic mice. Several mechanisms by which Bri2 can interfere with A beta production and aggregation have been proposed. Herein, we studied recombinant human Bri2 (residues 90-236) containing the extracellular Brichos domain without the ABri23 peptide. Bri2(90-236) binds to ABri23, which suggests that these two parts interact during Bri2 biosynthesis, in line with proposed functions of Brichos domains in other proteins. Moreover, Bri2(90-236) binds A beta 1-40 and inhibits its aggregation and fibril formation. These data suggest a model for how the processing of Bri2 and APP are interrelated. (C) 2009 Elsevier Inc. All rights reserved.
Alzheimer's disease; Brichos domain; Bri2; ITM2B; APP; Protein interaction
Biochemical and Biophysical Research Communications
2010, Volym: 393, nummer: 3, sidor: 356-361
Utgivare: ACADEMIC PRESS INC ELSEVIER SCIENCE
Biochemistry and Molecular Biology