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O1‐06‐04: Neuronal Function of the Amyloid Precursor Protein of Alzheimer's Disease
Author(s) -
Octave JeanNoel,
Santos Susana Ferrao,
Pierrot Nathalie,
Huysseune Sandra,
KienlenCampard Pascal
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.07.122
Subject(s) - amyloid precursor protein , small hairpin rna , microbiology and biotechnology , transfection , calcium , biology , gene expression , voltage dependent calcium channel , chemistry , gene , biochemistry , medicine , alzheimer's disease , rna , disease , organic chemistry
disease and offers ground for the development of a therapeutic strategy. As a first step for designing an inhibitor of Ab aggregation based on the mutated Ab sequence, we synthesized a peptide homologous to residues 1-6 of Ab with the A2 V substitution and tested its ability to bind to wild-type Ab and inhibit amyloidogenesis. The study showed that the mutated hexapeptide retains the anti-amyloidogenic properties of the parent full-length Ab. Molecular dynamics simulations suggest that this property may be related to the structural flexibility of the peptide that adopts dynamically ‘‘closed’’ and ‘‘open’’ configurations, at variance with the wild-type sequence which is characterized by a ‘‘closed’’ structure. Conclusion: The present data have important implications for genetic screening and the potential treatment of Alzheimer’s disease based on A2 V-modified Ab peptides or peptido-mimetic compounds.