Abstract
Alzheimer’s disease (AD) represents a neurological disorder, which is caused by enzymatic degradation of an amyloid precursor protein into short peptide fragments that undergo association to form insoluble plaques. Preliminary studies suggest that cyanobacterial extracts, especially the light-harvesting protein phycocyanin, may provide a means to control the progression of the disease. However, the molecular mechanism of disease control remains elusive. In the present study, intact hexameric phycocyanin was isolated and crystallized from the cyanobacterium Leptolyngbya sp. N62DM, and the structure was solved to a resolution of 2.6 A. Molecular docking studies show that the phycocyanin αβ- dimer interacts with the enzyme β-secretase, which catalyzes the proteolysis of the amyloid precursor protein to form plaques. The molecular docking studies suggest that the interaction between phycocyanin and β-secretase is energetically more favorable than previously reported inhibitor-β-secretase interactions. Transgenic Caenorhabditis elegans worms, with a genotype to serve as an AD-model, were significantly protected by phycocyanin. Therefore, the present study provides a novel structure-based molecular mechanism of phycocyanin-mediated therapy against AD.
Keywords: Alzheimer's, amyloid precursor protein, β-secretase, cyanobacteria, phycocyanin.
CNS & Neurological Disorders - Drug Targets
Title:Crystal Structure and Interaction of Phycocyanin with β-Secretase: A Putative Therapy for Alzheimer's Disease
Volume: 13 Issue: 4
Author(s): Niraj Kumar Singh, Syed S. Hasan, Jitendra Kumar, Isha Raj, Amrin A. Pathan, Asha Parmar, Shazi Shakil, Samudrala Gourinath and Datta Madamwar
Affiliation:
Keywords: Alzheimer's, amyloid precursor protein, β-secretase, cyanobacteria, phycocyanin.
Abstract: Alzheimer’s disease (AD) represents a neurological disorder, which is caused by enzymatic degradation of an amyloid precursor protein into short peptide fragments that undergo association to form insoluble plaques. Preliminary studies suggest that cyanobacterial extracts, especially the light-harvesting protein phycocyanin, may provide a means to control the progression of the disease. However, the molecular mechanism of disease control remains elusive. In the present study, intact hexameric phycocyanin was isolated and crystallized from the cyanobacterium Leptolyngbya sp. N62DM, and the structure was solved to a resolution of 2.6 A. Molecular docking studies show that the phycocyanin αβ- dimer interacts with the enzyme β-secretase, which catalyzes the proteolysis of the amyloid precursor protein to form plaques. The molecular docking studies suggest that the interaction between phycocyanin and β-secretase is energetically more favorable than previously reported inhibitor-β-secretase interactions. Transgenic Caenorhabditis elegans worms, with a genotype to serve as an AD-model, were significantly protected by phycocyanin. Therefore, the present study provides a novel structure-based molecular mechanism of phycocyanin-mediated therapy against AD.
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Singh Kumar Niraj, Hasan S. Syed, Kumar Jitendra, Raj Isha, Pathan A. Amrin, Parmar Asha, Shakil Shazi, Gourinath Samudrala and Madamwar Datta, Crystal Structure and Interaction of Phycocyanin with β-Secretase: A Putative Therapy for Alzheimer's Disease, CNS & Neurological Disorders - Drug Targets 2014; 13 (4) . https://dx.doi.org/10.2174/1871527313666140228114456
DOI https://dx.doi.org/10.2174/1871527313666140228114456 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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