title: Curcumin alters the salt bridge-containing turn region in amyloid β(1-42) aggregates.
abstract: Amyloid β (Aβ) fibrillar deposits in the brain are a hallmark of Alzheimer disease (AD). Curcumin, a common ingredient of Asian spices, is known to disrupt Aβ fibril formation and to reduce AD pathology in mouse models. Understanding the structural changes induced by curcumin can potentially lead to AD pharmaceutical agents with inherent bio-compatibility. Here, we use solid-state NMR spectroscopy to investigate the structural modifications of amyloid β(1-42) (Aβ42) aggregates induced by curcumin. We find that curcumin induces major structural changes in the Asp-23-Lys-28 salt bridge region and near the C terminus. Electron microscopy shows that the Aβ42 fibrils are disrupted by curcumin. Surprisingly, some of these alterations are similar to those reported for Zn(2+) ions, another agent known to disrupt the fibrils and alter Aβ42 toxicity. Our results suggest the existence of a structurally related family of quasi-fibrillar conformers of Aβ42, which is stabilized both by curcumin and by Zn(2+.)
authors.affiliation: Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005.
authors.forename: Venus Singh
authors.initials: VS
authors.lastname: Mithu
authors.affiliation: Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005.
authors.forename: Bidyut
authors.initials: B
authors.lastname: Sarkar
authors.affiliation: Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005.
authors.forename: Debanjan
authors.initials: D
authors.lastname: Bhowmik
authors.affiliation: Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005.
authors.forename: Anand Kant
authors.initials: AK
authors.lastname: Das
authors.affiliation: Department of Biochemistry, Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, A. D. Marg, Parel, Mumbai 400012, and.
authors.forename: Muralidharan
authors.initials: M
authors.lastname: Chandrakesan
authors.affiliation: Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005,. Electronic address: maiti@tifr.res.in.
authors.forename: Sudipta
authors.initials: S
authors.lastname: Maiti
authors.affiliation: Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005,; Tata Institute of Fundamental Research Centre for Interdisciplinary Sciences, 21 Brundavan Colony, Narsinghi, Hyderabad 500 075, India. Electronic address: madhu@tifr.res.in.
authors.forename: Perunthiruthy K
authors.initials: PK
authors.lastname: Madhu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003474:Curcumin / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D055550:Protein Stability; D017433:Protein Structure, Secondary; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D003474:Curcumin; D015032:Zinc
keywords: Alzheimer Disease; Amyloid; Drug Action; Magic-angle Spinning; NMR; Protein Aggregation; Salt Bridge; Solid State NMR