Properties of neurotoxic peptides related to the BRI gene.
Mutations in the BRI gene are thought to cause dementias in members of families. The clinical symptoms are similar to those of Alzheimer's disease, but with additional ocular and hearing deficits, and spasticity. The mutations lead to the release of the 34-residue peptides, ABri and ADan, in the brains of afflicted individuals. We have synthesized the peptides in their straight-chain and oxidized cyclic forms and shown that the oxidized form of ABri and reduced form of ADan are toxic to human neuronal cell lines in culture. Neurotoxicity correlates with the extent of formation of SDS-stable non-fibrillar low-molecular-mass oligomers (SSNFOs).
Neurodegeneration Unit, Surgery Department, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK. sghk200@sghms.a.cuk
B
B
Austen
O
O
el-Agnaf
S
S
Nagala
B
B
Patel
N
N
Gunasekera
M
M
Lee
V
V
Lelyveld
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000235:genetics* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003704:Dementia / Q000235:genetics*; D003718:Denmark; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009498:Neurotoxins / Q000737:chemistry / Q000633:toxicity*; D010446:Peptide Fragments / Q000633:toxicity*; D006113:United Kingdom
D048868:Adaptor Proteins, Signal Transducing; D000682:Amyloid; C120083:ITM2B protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009498:Neurotoxins; D010446:Peptide Fragments; D007770:L-Lactate Dehydrogenase