TY - JOUR
T1 - 5-HT6 Receptor Agonist and Antagonist Against β-Amyloid-Peptide-Induced Neurotoxicity in PC-12 Cells
AU - Bokare, Anand M.
AU - Praveenkumar, A. K.
AU - Bhonde, Mandar
AU - Nayak, Yogendra
AU - Pal, Ravindra
AU - Goel, Rajan
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Beta-amyloid peptide (Aβ) induced neurotoxicity is considered as a hallmark of the pathogenesis of Alzheimer’s disease (AD). The present study demonstrated the neuroprotective role of 5-HT6 receptors against Aβ-induced neurotoxicity in PC-12 cells. The 5-HT6 receptor agonist EMD-386088 and antagonist SB-399885 were used as pharmacological tools. The NMDA receptor antagonist, memantine, was used as reference standard. The Aβ25−35 (50 µM) induced apoptosis, increased reactive oxygen species (ROS) generation and impaired neurite outgrowth in PC-12 cells. Pre-treatment with 10 µM EMD-386088 and SB-399885 had significantly protected neuronal cell death by maintaining higher cell viability through attenuation of intracellular ROS. Further, both compounds significantly prevented Aβ25−35-induced impairment in neurite outgrowth in PC-12 cells. Similarly, memantine prevented Aβ25−35-induced neurotoxicity in PC-12 cells. These findings suggest that 5-HT6 receptor ligands have protected neurons from Aβ25−35 induced toxicity by reducing ROS and through prevention of impairment in neurite outgrowth. Therefore, 5-HT6 receptor could be an important disease-modifying therapeutic target for AD.
AB - Beta-amyloid peptide (Aβ) induced neurotoxicity is considered as a hallmark of the pathogenesis of Alzheimer’s disease (AD). The present study demonstrated the neuroprotective role of 5-HT6 receptors against Aβ-induced neurotoxicity in PC-12 cells. The 5-HT6 receptor agonist EMD-386088 and antagonist SB-399885 were used as pharmacological tools. The NMDA receptor antagonist, memantine, was used as reference standard. The Aβ25−35 (50 µM) induced apoptosis, increased reactive oxygen species (ROS) generation and impaired neurite outgrowth in PC-12 cells. Pre-treatment with 10 µM EMD-386088 and SB-399885 had significantly protected neuronal cell death by maintaining higher cell viability through attenuation of intracellular ROS. Further, both compounds significantly prevented Aβ25−35-induced impairment in neurite outgrowth in PC-12 cells. Similarly, memantine prevented Aβ25−35-induced neurotoxicity in PC-12 cells. These findings suggest that 5-HT6 receptor ligands have protected neurons from Aβ25−35 induced toxicity by reducing ROS and through prevention of impairment in neurite outgrowth. Therefore, 5-HT6 receptor could be an important disease-modifying therapeutic target for AD.
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U2 - 10.1007/s11064-017-2217-9
DO - 10.1007/s11064-017-2217-9
M3 - Article
AN - SCOPUS:85014517523
SN - 0364-3190
VL - 42
SP - 1571
EP - 1579
JO - Neurochemical Research
JF - Neurochemical Research
IS - 5
ER -