Abeta(25-35) And Its C- And/Or N-Blocked Derivatives: Copper Driven Structural Features And Neurotoxicity(760 views) Giuffrida ML, Grasso G, Ruvo M, Pedone C, Saporito A, Marasco D, Pignataro B, Cascio C, Copani A, Rizzarelli E
Journal Of Neuroscience Research (ISSN: 0360-4012), 2007 Feb 15; 85(3): 623-633.
Keywords: β-Amyloid, Alzheimer, S Disease, Copper, Fibrils, Folding, Amyloid Beta Protein[25-35], Trace Metal, Amyloid Beta Protein (25 35), Amyloid Beta-Protein (25-35), Neurotoxin, Peptide Fragment, Unclassified Drug, Alzheimer Disease, Amino Terminal Sequence, Animal Cell, Article, Controlled Study, Electron Spin Resonance, Electrospray Mass Spectrometry, Neurotoxicity, Nonhuman, Oligomerization, Priority Journal, Protein Structure, Protein Synthesis, Scanning Force Microscopy, Animal Model, Atomic Force Microscopy, Brain Cortex, Chemistry, Circular Dichroism, Drug Effect, Nerve Cell, Pathology, Protein Conformation, Cerebral Cortex, Electron Spin Resonance Spectroscopy, Electrospray Ionization, Amyloid Beta Protein [25-35],
Affiliations: *** IBB - CNR ***
PhD Program in Neurobiology, Faculty of Medicine, University of Catania, Catania, Italy
I.B.B., CNR, Catania, Italy
I.B.B., CNR, Napoli, Italy
Department of Physical-Chemistry (F. Accascina), University of Palermo, Palermo, Italy
Consorzio Catania Ricerche, Catania, Italy
Department of Pharmaceutical Sciences, University of Catania, Catania, Italy
Department of Chemical Sciences, University of Catania, Catania, Italy
I. B. B., CNR, Catania, Italy
I. B. B., CNR, Napoli, Italy
References: Not available.
Abeta(25-35) And Its C- And/Or N-Blocked Derivatives: Copper Driven Structural Features And Neurotoxicity
The toxic properties of P-amyloid protein, A beta (1-42), the major component of senile plaques in Alzheimer's disease, depend on nucleation-dependent oligomerization and aggregation. In addition, A beta (1-42) toxicity is favored by the presence of trace metals, which affect the secondary structure of the peptide. A peptide comprising 11 residues within A beta (1-42) [A beta (25-35)] aggregates and retains the neurotoxic activity of A beta (1-42). We have used both A beta (25-35) and its C-amidated or N-acetylated/C-amidated derivatives to investigate the role of copper (II) in modulating the conformation and aggregation state as well as the neurotoxic properties of amyloid peptides. Electrospray ionization mass spectrometry (ESI-MS) and electron paramagnetic resonance (EPR) measurements were performed to verify the formation of copper (II) /A beta (25-35) complexes and to determine the coordination mode, respectively. A beta (2535) and its derivatives were analyzed by circular dichroism spectroscopy to assess their secondary structure, subjected to thioflavine-T (Th-T) binding assay to reveal beta-sheet structured aggregates formation, and imaged by scanning force microscopy. Toxicity was assessed on mature cultures of rat cortical neurons. We found that beta-sheet-structured species of A beta (25-35) were neurotoxic, whereas the random-coil-structured derivatives were devoid of effect. Interestingly, copper promoted the random-coiI/beta-sheet transition of A beta (25-35), with ensuing peptide toxicity, but it induced the toxicity of the N-acetylated/C-amidated derivative without affecting peptide folding. Moreover, copper did not influence either the folding or the activity of the C-amidated A beta (25-35), suggesting that blockade of the C-terminus of A beta peptides might be sufficient to prevent A beta toxicity. (c) 2006 Wiley-Liss, Inc
Abeta(25-35) And Its C- And/Or N-Blocked Derivatives: Copper Driven Structural Features And Neurotoxicity
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Abeta(25-35) And Its C- And/Or N-Blocked Derivatives: Copper Driven Structural Features And Neurotoxicity