Related Experiment Video
Updated: May 23, 2025
08:49
Rapid In Situ Hybridization using Oligonucleotide Probes on Paraformaldehyde-prefixed Brain of Rats with Serotonin Syndrome
Published on: September 23, 2015
8.8K
Novel 5-HT6R modulators as mTOR-dependent neuronal autophagy inductors.
José Miguel Alcaíno1, Gonzalo Vera2, Gonzalo Almarza1
1Laboratorio de Fisiología y Bioenergética Celular, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago, 7810000, Chile.
Scientific Reports
|March 12, 2025
Summary
New compounds PUC-10 and PUC-55 activate autophagy by inhibiting the mTOR pathway. This discovery offers potential therapeutic strategies for neurological disorders by targeting the 5-HT6 receptor.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Autophagy is a cellular degradation process regulated by the mTOR pathway.
- The 5-HT6 receptor is implicated in cognitive functions and linked to the mTOR pathway.
Purpose of the Study:
- To investigate novel 5-HT6 receptor antagonists for potential cognitive enhancement.
- To explore the mechanism of action of these antagonists in inducing autophagy via mTOR inhibition.
Main Methods:
- Design and synthesis of 5-HT6 receptor antagonists (PUC-10 and PUC-55).
- Assessment of binding affinity, antagonist potency, and cellular viability.
- Evaluation of autophagy induction and mTOR pathway inhibition in SH-SY5Y neuroblastoma cells.
Main Results:
- PUC-10 and PUC-55 demonstrated high affinity and potency as 5-HT6 receptor antagonists.
- Both compounds effectively induced mTOR-dependent autophagy with high cellular viability.
- Unlike Rapamycin, PUC-10 and PUC-55 led to 5-HT6 receptor overexpression.
Conclusions:
- PUC-10 and PUC-55 are novel 5-HT6 receptor antagonists that induce autophagy by inhibiting the mTOR pathway.
- These compounds show promise as potential therapeutics for neurological disorders.
