5-HT6 Receptor Agonist and Antagonist Against [beta]-Amyloid-Peptide-Induced Neurotoxicity in PC-12 Cells

• Published in: Neurochemical research 2017-05, Vol.42 (5), p.1571
• Main Authors: Bokare, Anand M, Praveenkumar, A K, Bhonde, Mandar, Nayak, Yogendra, Pal, Ravindra, Goel, Rajan
• Format: Article
• Language: English
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-017-2217-9

Beta-amyloid peptide (A[beta]) 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 A[beta]-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 A[beta]25-35 (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 A[beta]25-35-induced impairment in neurite outgrowth in PC-12 cells. Similarly, memantine prevented A[beta]25-35-induced neurotoxicity in PC-12 cells. These findings suggest that 5-HT6 receptor ligands have protected neurons from A[beta]25-35 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.