I32E and V36K double mutation in beta2-sheet abrogates amyloid beta peptide toxicity.
Alzheimer's disease (AD) is the most common cause of dementia in the elderly, wherein, the accumulation of amyloid beta (Abeta) peptide as cytotoxic oligomers leads to neuropathologic changes. Transgenic mice with brain Abeta plaques immunized with aggregated Abeta have reduced amyloid burden and improved cognitive functions. However, such active immunization in humans led to a small but significant occurrence of meningoencephalitis in 6% AD volunteers due to Abeta induced toxicity. In an attempt to develop safer alternative vaccines, the design of a highly soluble peptide homologous to Abeta (Abeta-EK), that has a reduced amyloidogenic potential while maintaining the major immunogenic epitopes of Abeta is reported. More importantly, this homologue has been shown to be non-toxic, as this peptide failed to exert any observable effect on erythrocytes. The results of the present study suggests that immunization with non-toxic Abeta derivative may offer a safer therapeutic approach to AD, instead of using toxic Abeta fibrils.
Department of Neurochemistry, National Institute of Mental Health & Neurosciences, Bangalore 560 029, India. sarada@nimhans.kar.nic.in
Sarada
S
Subramanian
Pradeep Kumar
PK
Mishra
Debashree
D
Bandopadhyay
D000544:Alzheimer Disease / Q000276:immunology / Q000517:prevention & control; D023582:Alzheimer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000918:Antibody Specificity; D052160:Benzothiazoles; D048430:Cell Shape / Q000187:drug effects / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D011817:Rabbits; D013844:Thiazoles / Q000378:metabolism
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D013844:Thiazoles; C009462:thioflavin T