In vitro neurotoxicity of amyloid β-peptide cross-linked by transglutaminase.
Abstract
Transglutaminase catalyzes the intermolecular cross-linking of peptides between Gln and Lys residues, forming an ε-(γ-glutamyl) lysine bond. Amyloid β-peptide, a major constituent of the deposits in Alzheimer disease, contains Lys16, Lys28, and Gln15 which may act as substrates of transglutaminase. Transglutaminase treatment of amyloid β-peptide (1-28) and amyloid β-peptide (1-40) yielded cross-linked oligomers. Transglutaminase-treated Aβ retarded neurite extension of PC12 cells, and rat cultured neurons of hippocampus and septum, brain areas severely affected by Alzheimer disease, and subsequently caused cell death, whereas the transglutaminase-untreated counterparts did not show harmful effects. The transglutaminase-catalyzed oligomers of amyloid β-peptide and their neurotoxicity may be involved in two characteristics in Alzheimer disease, neuronal degeneration and formation of the insoluble deposits. AD - Alzheimer disease, Aβ - amyloid β-peptide, DMEM - Dulbecco's modified Eagle's medium, DMEM/F-12-1:1 mixture of DMEM and Ham's F-12 medium, FCS - fetal calf serum, HS - horse serum, PAGE - polyacrylamide gel electrophoresis, MTT - 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, NGF - nerve growth factor, TGase...Continue Reading
References
Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein
Citations
Related Concepts
Related Feeds
Alzheimer's Disease: Amyloid Beta
Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.
Alzheimer's Disease: APP
Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.