Journal ArticleDOI
Copper Mediates Dityrosine Cross-Linking of Alzheimer's Amyloid-β
Craig S. Atwood,Craig S. Atwood,Craig S. Atwood,George Perry,Hong Zeng,Yoji Kato,Walton D. Jones,Ke Qing Ling,Xudong Huang,Robert D. Moir,Dandan Wang,Lawrence M. Sayre,Mark A. Smith,Shu G. Chen,Ashley I. Bush,Ashley I. Bush +15 more
TLDR
The results suggest that Cu interactions with Abeta could be responsible for causing the covalent cross-linking of Abeta in these structures.Abstract:
We have previously reported that amyloid Abeta, the major component of senile plaques in Alzheimer's disease (AD), binds Cu with high affinity via histidine and tyrosine residues [Atwood, C. S., et al. (1998) J. Biol. Chem. 273, 12817-12826; Atwood, C. S., et al. (2000) J. Neurochem. 75, 1219-1233] and produces H(2)O(2) by catalyzing the reduction of Cu(II) or Fe(III) [Huang, X., et al. (1999) Biochemistry 38, 7609-7616; Huang, X., et al. (1999) J. Biol. Chem. 274, 37111-37116]. Incubation with Cu induces the SDS-resistant oligomerization of Abeta [Atwood, C. S., et al. (2000) J. Neurochem. 75, 1219-1233], a feature characteristic of neurotoxic soluble Abeta extracted from the AD brain. Since residues coordinating Cu are most vulnerable to oxidation, we investigated whether modifications of these residues were responsible for Abeta cross-linking. SDS-resistant oligomerization of Abeta caused by incubation with Cu was found to induce a fluorescence signal characteristic of tyrosine cross-linking. Using ESI-MS and a dityrosine specific antibody, we confirmed that Cu(II) (at concentrations lower than that associated with amyloid plaques) induces the generation of dityrosine-cross-linked, SDS-resistant oligomers of human, but not rat, Abeta peptides. The addition of H2O2 strongly promoted Cu-induced dityrosine cross-linking of Abeta1-28, Abeta1-40, and Abeta1-42, suggesting that the oxidative coupling is initiated by interaction of H2O2 with a Cu(II) tyrosinate. The dityrosine modification is significant since it is highly resistant to proteolysis and is known to play a role in increasing structural strength. Given the elevated concentration of Cu in senile plaques, our results suggest that Cu interactions with Abeta could be responsible for causing the covalent cross-linking of Abeta in these structures.read more
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The neurobiology of zinc in health and disease
TL;DR: The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC, and the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'.
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Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases
TL;DR: Evidence for the potential role of curcumin in the prevention and treatment of various proinflammatory chronic diseases is provided and its features, combined with the pharmacological safety and negligible cost, renderCurcumin an attractive agent to explore further.
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Copper Homeostasis and Neurodegenerative Disorders (Alzheimer's, Prion, and Parkinson's Diseases and Amyotrophic Lateral Sclerosis)
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Oxidative stress and the amyloid beta peptide in Alzheimer's disease.
Clémence Cheignon,M. Tomas,M. Tomas,Dominique Bonnefont-Rousselot,Peter Faller,Christelle Hureau,Christelle Hureau,Fabrice Collin,Fabrice Collin +8 more
TL;DR: This review highlights the existing link between oxidative stress and AD, and the consequences towards the Aβ peptide and surrounding molecules in terms of oxidative damage, along with the implication of metal ions in AD.
Journal ArticleDOI
Metals in Alzheimer's and Parkinson's Diseases
TL;DR: There has been steadily growing interest in the participation of metal ions in neurobiological processes, such as the regulation of synaptic transmission, and increasingly sophisticated medicinal chemistry approaches, which correct these metal abnormalities without causing systemic disturbance of these essential minerals, show promise of being disease-modifying.
References
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Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein
George G. Glenner,Caine W. Wong +1 more
TL;DR: A purified protein derived from the twisted beta-pleated sheet fibrils in cerebrovascular amyloidosis associated with Alzheimer's disease has been isolated and Amino acid sequence analysis and a computer search reveals this protein to have no homology with any protein sequenced thus far.
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The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Jie Kang,H. G. Lemaire,A. Unterbeck,J. M. Salbaum,Colin L. Masters,K.-H. Grzeschik,Gerd Multhaup,Konrad Beyreuther,Benno Müller-Hill +8 more
TL;DR: An apparently full-length complementary DNA clone coding for the A4 polypeptide is isolated and sequenced and suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor.
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Amyloid plaque core protein in Alzheimer disease and Down syndrome
Colin L. Masters,Gail Simms,Nicola A. Weinman,Gerd Multhaup,Brian L. McDonald,Konrad Beyreuther +5 more
TL;DR: The shared 4-kDa subunit indicates a common origin for the amyloids of the plaque core and of the congophilic angiopathy of Alzheimer disease and Down syndrome.
Journal ArticleDOI
Alzheimerʼs disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein
G G Glenner,C W Wong +1 more
TL;DR: A purified protein derived from the twisted beta-pleated sheet fibrils in cerebrovascular amyloidosis associated with Alzheimer's disease has been isolated and Amino acid sequence analysis and a computer search reveals this protein to have no homology with any protein sequenced thus far.
Journal ArticleDOI
Copper, iron and zinc in Alzheimer's disease senile plaques
TL;DR: Concentrations of copper (Cu), iron (Fe) and zinc (Zn) were measured in the rims and cores of senile plaques (SP) and in the neuropil of the amygdala of nine Alzheimer's disease patients and in that of five neurologically normal control subjects using micro particle-induced X-ray emission (micro-PIXE).
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