5-HT6 receptor agonist and antagonist against β-Amyloid-Peptide-Induced neurotoxicity in PC-12 cells

Nayak, Yogendra (2017) 5-HT6 receptor agonist and antagonist against β-Amyloid-Peptide-Induced neurotoxicity in PC-12 cells. Neurochemical Research, 42 (5). pp. 1571-1579. ISSN 0364-3190

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: 5-HT6 receptor; PC-12 cells; Aβ25−35; Neuroprotection; Alzheimer’s disease.
Subjects: Pharmacy > MCOPS Manipal > Pharmacology
Depositing User: KMC Library
Date Deposited: 08 Jun 2017 11:15
Last Modified: 08 Jun 2017 11:15
URI: http://eprints.manipal.edu/id/eprint/149017

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