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Studies on the Role of Amino Acid Stereospecificity in Amyloid Beta Aggregation

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Abstract

Amyloid beta (Aβ) deposition and neurodegeneration are the two related events in the pathogenesis of Alzheimer’s disease. Several factors modulate the conformation and physical properties of Aβ, which in turn affects its biological functions. Among these, age-dependent changes in the stereospecificity of the amino acids comprising Aβ is one such factors. In the present study, we investigated the aggregation property of Aβ as a function of the stereospecificity of amino acids comprising the peptide. We carried out our study by comparing the physical properties of Aβ(1-40) all-L and Aβ(1-40) all-D enantiomers using various biophysical techniques. These results indicated that the aggregation and folding parameters of Aβ are stereospecific and the aggregation property strongly depends upon the amino acid sequence and their stereospecificity. This may possibly help to understand the stereospecific role of amino acids comprising Aβ in its aggregation and its relevance to neurodegeneration.

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Abbreviations

AD:

Alzheimer’s disease

Aβ:

amyloid beta

Aβ(1-40) all-L:

amyloid beta peptide consisting of all L-amino acids

Aβ(1-40) all-D:

amyloid beta peptide consisting of all d-amino acids

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Acknowledgment

The authors are indebted to Dr. V. Prakash, Director, Central Food Technological Research Institute, Mysore, for all his support and encouragement. Veer Bala is thankful to the Indian Council of Medical Research (ICMR) for awarding senior research fellowship. This work was supported by the grant from the Department of Biotechnology, Delhi, India. We profoundly thank Dr. Rivka Ravid, Senior Advisor, Netherlands Brain Bank, Amsterdam, The Netherlands, for reviewing the manuscript and for providing the valuable suggestions. The work is supported by CFTRI inhouse project NNP-040 also.

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Authors and Affiliations

  1. Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, 570020, India

    Veer Bala Gupta & K. S. J. Rao

  2. Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India

    S. S. Indi

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  1. Veer Bala Gupta
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  2. S. S. Indi
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  3. K. S. J. Rao
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Correspondence to K. S. J. Rao.

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Gupta, V.B., Indi, S.S. & Rao, K.S.J. Studies on the Role of Amino Acid Stereospecificity in Amyloid Beta Aggregation. J Mol Neurosci 34, 35–43 (2008). https://doi.org/10.1007/s12031-007-0070-z

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  • DOI: https://doi.org/10.1007/s12031-007-0070-z

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