Therapeutic potential of cyanobacterial pigment protein phycoerythrin: in silico and in vitro study of BACE1 interaction and in vivo Aβ reduction
Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid
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Yn: International journal of biological macromolecules, Cyfrol 134, 01.08.2019, t. 368-378.
Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid
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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 -