Neuroprotective Role of Fenchol in Modulating the B-CSF Barrier in Neurodegenerative Diseases

Overview

Current underlying mechanisms to treat neurodegenerative diseases (ND) are limited due to an incomplete understanding. Tight junctions (TJ) and efflux pumps on the BBB restrict drug permeability, causing a major limitation in current treatments which prevents therapeutic agents from reaching neurons. However, the blood-cerebrospinal fluid barrier (B-CSFB) is a potential alternative route for the clearance of toxins associated with ND since it's more accessible with fewer efflux pumps on membranes. A permeability increase in B-CSFB in ND patients causes inflammatory toxins, such as lipopolysaccharides (LPS) to enter the brain, contributing to neurodegeneration. This study aimed to determine whether fenchol improves the integrity of the B-CSFB after LPS challenge through the regulation of i) TJs, ii) inflammatory cytokines, and iii) cell viability. LPS significantly decreased the expression of TJ proteins, Ocln (p<0.01), and ZO-1 (p<0.001). While fenchol didn't prevent TJ downregulation (p>0.05), butyrate treatment improved TJ expression in LPS-treated cells (p<0.01). LPS didn't cause a notable change in IL-6 or IL-1ß expression (p>0.05). This suggests it may not play a role in inflammation in NDs. In comparison to the control group, fenchol reduced inflammatory gene expression. suggesting a role in preventing inflammatory conditions (p>0.05). 24 hours after LPS treatment, cell viability decreased (p<0.01). However, butyrate protected cells against LPS-induced cell death (p<0.0001), whereas fenchol exacerbated this effect, suggesting butyrate and fenchol as a combination therapy may have synergistic effects. This project is the first to establish fenchol's potential as a natural-based treatment, expediting approval pathways for plant-derived neuroprotective agents.

Competition history

• ISEF 2025 Cellular and Molecular Biology · Entry CELL005

Resources

• ISEF abstract page ↗

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