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

Anand M. Bokare, A. K. Praveenkumar, Mandar Bhonde, Yogendra Nayak, Ravindra Pal, Rajan Goel

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1571-1579
Number of pages9
JournalNeurochemical Research
Volume42
Issue number5
DOIs
Publication statusPublished - 01-05-2017

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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