miR-424-5p maybe regulate blood-brain barrier permeability in a model in vitro with Abeta incubated endothelial cells

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• The blood-brain barrier (BBB) integrity is compromised in Alzheimer's disease (AD), but the underlying molecular mechanisms remain largely unknown.
• MicroRNAs (miRNAs) are implicated in regulating gene expression and cellular functions relevant to AD pathogenesis.

Purpose of the Study:

• To investigate the role of miR-424-5p in regulating BBB permeability in an in vitro AD model.
• To elucidate the molecular targets and pathways affected by miR-424-5p in brain endothelial cells.

Main Methods:

• Upregulation of miR-424-5p in Abeta-treated microvascular endothelial cells was confirmed.
• Transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) exudation assays were used to assess BBB permeability.
• Western blotting and dual-luciferase reporter assays were employed to analyze protein expression and miRNA-target interactions.

Main Results:

• Silencing miR-424-5p significantly decreased BBB permeability in Abeta-treated endothelial cells.
• MiR-424-5p silencing led to the upregulation of tight junction proteins ZO-1 and occludin.
• Endophilin-1 was identified as a direct target of miR-424-5p, and its expression was restored upon miR-424-5p silencing.

Conclusions:

• MiR-424-5p contributes to increased BBB permeability in AD by downregulating Endophilin-1 and subsequently affecting tight junction proteins.
• Targeting miR-424-5p represents a potential therapeutic strategy for preserving BBB function in Alzheimer's disease.