TY - JOUR
T1 - Identification of Caffeic Acid Phenethyl Ester (CAPE) as a Potent Neurodifferentiating Natural Compound That Improves Cognitive and Physiological Functions in Animal Models of Neurodegenerative Diseases
AU - Konar, Arpita
AU - Kalra, Rajkumar Singh
AU - Chaudhary, Anupama
AU - Nayak, Aashika
AU - Guruprasad, Kanive P.
AU - Satyamoorthy, Kapaettu
AU - Ishida, Yoshiyuki
AU - Terao, Keiji
AU - Kaul, Sunil C.
AU - Wadhwa, Renu
N1 - Funding Information:
Funding. The present study was supported by grants from the Department of Biotechnology (Government of India), Department of Science and Technology (Government of India; DST/INSPIRE/04/2014/002261) and AIST (Japan).
Publisher Copyright:
© Copyright © 2020 Konar, Kalra, Chaudhary, Nayak, Guruprasad, Satyamoorthy, Ishida, Terao, Kaul and Wadhwa.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11/10
Y1 - 2020/11/10
N2 - Cell-based screening of bioactive compounds has served as an important gateway in drug discovery. In the present report, using human neuroblastoma cells and enrolling an extensive three-step screening of 57 phytochemicals, we have identified caffeic acid phenethyl ester (CAPE) as a potent neurodifferentiating natural compound. Analyses of control and CAPE-induced neurodifferentiated cells revealed: (i) modulation of several key proteins (NF200, MAP-2, NeuN, PSD95, Tuj1, GAP43, and GFAP) involved in neurodifferentiation process; and (ii) attenuation of neuronal stemness (HOXD13, WNT3, and Msh-2) and proliferation-promoting (CDC-20, CDK-7, and BubR1) proteins. We anticipated that the neurodifferentiation potential of CAPE may be beneficial for the treatment of neurodegenerative diseases and tested it using the Drosophila model of Alzheimer’s disease (AD) and mice model of amnesia/loss of memory. In both models, CAPE exhibited improved disease symptoms and activation of physiological functions. Remarkably, CAPE-treated mice showed increased levels of neurotrophin-BDNF, neural progenitor marker-Nestin, and differentiation marker-NeuN, both in the cerebral cortex and hippocampus. Taken together, we demonstrate the differentiation-inducing and therapeutic potential of CAPE for neurodegenerative diseases.
AB - Cell-based screening of bioactive compounds has served as an important gateway in drug discovery. In the present report, using human neuroblastoma cells and enrolling an extensive three-step screening of 57 phytochemicals, we have identified caffeic acid phenethyl ester (CAPE) as a potent neurodifferentiating natural compound. Analyses of control and CAPE-induced neurodifferentiated cells revealed: (i) modulation of several key proteins (NF200, MAP-2, NeuN, PSD95, Tuj1, GAP43, and GFAP) involved in neurodifferentiation process; and (ii) attenuation of neuronal stemness (HOXD13, WNT3, and Msh-2) and proliferation-promoting (CDC-20, CDK-7, and BubR1) proteins. We anticipated that the neurodifferentiation potential of CAPE may be beneficial for the treatment of neurodegenerative diseases and tested it using the Drosophila model of Alzheimer’s disease (AD) and mice model of amnesia/loss of memory. In both models, CAPE exhibited improved disease symptoms and activation of physiological functions. Remarkably, CAPE-treated mice showed increased levels of neurotrophin-BDNF, neural progenitor marker-Nestin, and differentiation marker-NeuN, both in the cerebral cortex and hippocampus. Taken together, we demonstrate the differentiation-inducing and therapeutic potential of CAPE for neurodegenerative diseases.
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U2 - 10.3389/fnagi.2020.561925
DO - 10.3389/fnagi.2020.561925
M3 - Article
AN - SCOPUS:85096638435
SN - 1663-4365
VL - 12
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
M1 - 561925
ER -