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New Hope for the Diagnosis and Therapy of Alzheimer's Disease

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Improperly folded metal cofactor-containing proteins (e.g., copper chaperone for superoxide dismutase, CCS) are believed to play a key role in several protein-misfolding diseases (e.g., Alzheimer's disease or Amyotrophic Lateral Sclerosis) because under regular physiological conditions, metallochaperones activate or stabilize the native conformation of important metalloproteins (e.g., superoxide dismutase) in certain cellular processes. For an improved diagnosis and therapy of neurodegenerative diseases, new methodologies have to be developed that enable a well-defined differentiation between properly folded and inactive metalloproteins in clinical samples. In the literature it is reported that different high molecular mass metal-containing proteins were isolated in brain samples from Alzheimer's patients and in vegetables by using a 2-dimensional polyacrylamide gel electrophoresis (2-DE) procedure. In the present article, selected results of these studies are scrutinized and compared with some results obtained by a standardized method termed ‘quantitative preparative native continuous polyacrylamide gel electrophoresis (QPNC-PAGE)’. Conclusively, QPNC-PAGE is a highly efficient approach used by biochemists to resolve native and denatured metalloproteins (MW 6 - ≥ 200 kDa) in complex protein mixtures.

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Keywords: 2-DE; Alzheimer's disease; CCS; GPC; NMR; QPNC-PAGE; biofluids; breakthrough method; isoelectric point; native conformation

Document Type: Research Article

Affiliations: Institute for Chemistry and Dynamics of the Geosphere, Institute 3: Phytosphere, Research Center Juelich, Juelich 52425, Germany.

Publication date: 01 April 2007

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  • Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.
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