TY - JOUR

T1 - Therapeutic potential of cyanobacterial pigment protein phycoerythrin

T2 - in silico and in vitro study of BACE1 interaction and in vivo Aβ reduction

AU - Chaubey, Mukesh Ghanshyam

AU - Patel, Stuti Nareshkumar

AU - Rastogi, Rajesh Prasad

AU - Srivastava, Prabhakar Lal

AU - Singh, Arun Kumar

AU - Madamwar, Datta

AU - Singh, Niraj Kumar

N1 - Copyright © 2019 Elsevier B.V. All rights reserved.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Cyanobacteria are an immense source of innovative classes of pharmacologically active compounds exhibiting various biological activities ranging from antioxidants, antibiotics, anticancer, anti-inflammatory to anti-Alzheimer's disease. In the present study, we primarily targeted the inhibition of Beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) by a naturally occurring cyanobacterial protein phycoerythrin (C-PE). BACE1 cleaves amyloid-β precursor protein (APP) and leads to accumulation of neurotoxic amyloid beta (Aβ) plaques in the brain, as an attribute of Alzheimer's disease (AD). Inhibition of BACE1 was measured in terms of their association and dissociation rate constants, thermodynamics of binding using surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). The kinetic parameters for enzyme activity were also measured using synthetic decapeptide as a substrate. We further validated the potential of PE by in-vivo histopathological staining of Aβ aggregate mutant Caenorhabditis elegans CL4176 by Thioflavin-T. The present studies pave the way for the application of naturally occurring C-PE as a putative therapeutic drug for the AD.

AB - Cyanobacteria are an immense source of innovative classes of pharmacologically active compounds exhibiting various biological activities ranging from antioxidants, antibiotics, anticancer, anti-inflammatory to anti-Alzheimer's disease. In the present study, we primarily targeted the inhibition of Beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) by a naturally occurring cyanobacterial protein phycoerythrin (C-PE). BACE1 cleaves amyloid-β precursor protein (APP) and leads to accumulation of neurotoxic amyloid beta (Aβ) plaques in the brain, as an attribute of Alzheimer's disease (AD). Inhibition of BACE1 was measured in terms of their association and dissociation rate constants, thermodynamics of binding using surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). The kinetic parameters for enzyme activity were also measured using synthetic decapeptide as a substrate. We further validated the potential of PE by in-vivo histopathological staining of Aβ aggregate mutant Caenorhabditis elegans CL4176 by Thioflavin-T. The present studies pave the way for the application of naturally occurring C-PE as a putative therapeutic drug for the AD.

KW - Amyloid Precursor Protein Secretases/chemistry

KW - Amyloid beta-Peptides/chemistry

KW - Animals

KW - Aspartic Acid Endopeptidases/chemistry

KW - Caenorhabditis elegans

KW - Cyanobacteria/chemistry

KW - Enzyme Activation

KW - Humans

KW - Immunohistochemistry

KW - Kinetics

KW - Molecular Conformation

KW - Molecular Docking Simulation

KW - Molecular Dynamics Simulation

KW - Phycoerythrin/chemistry

KW - Protein Binding

KW - Protein Refolding

KW - Recombinant Proteins

KW - Structure-Activity Relationship

U2 - 10.1016/j.ijbiomac.2019.05.006

DO - 10.1016/j.ijbiomac.2019.05.006

M3 - Article

C2 - 31059742

VL - 134

SP - 368

EP - 378

JO - International journal of biological macromolecules

JF - International journal of biological macromolecules

SN - 0141-8130

ER -