title: Self-assembly of stable oligomeric and fibrillar aggregates of Aβ peptides relevant to Alzheimer's disease: morphology dependent Cu/heme toxicity and inhibition of PROS generation.
abstract: Large and small aggregates of Aβ peptides, resembling the morphology and dimensions of fibrillar and oligomeric forms of Aβ respectively, relevant to Alzheimer's disease, are stabilized on electrodes using self-assembly. Both of these forms were found to bind redox active Cu and heme, resulting in active sites having distinctive biophysical properties. The reduced metal bound Aβ active sites of both the oligomeric and fibrillar forms of Aβ produce detrimental partially reduced oxygen species (PROS). While the larger aggregates of heme-Aβ produce more PROS in situ, the smaller aggregates of Cu-Aβ produce more PROS. 8-Hydroxy quinoline and methylene blue are inhibitors of Cu and heme bound Aβ respectively, and are shown to efficiently reduce PROS formation in the oligomeric forms. However, these inhibitors are ineffective in reducing the toxicities of the Cu and heme bound Aβ peptides in the fibrils, making them significantly more lethal than the smaller Aβ aggregates.
authors: Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India. icad@iacs.res.in icsgd@iacs.res.in.
authors: Kushal
authors: K
authors: Sengupta
authors: Sudipta
authors: S
authors: Chatterjee
authors: Debajyoti
authors: D
authors: Pramanik
authors: Somdatta Ghosh
authors: SG
authors: Dey
authors: Abhishek
authors: A
authors: Dey
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D003300:Copper / Q000737:chemistry / Q000633:toxicity*; D006418:Heme / Q000737:chemistry / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D017382:Reactive Oxygen Species; D006418:Heme; D003300:Copper