Technologies

A Potent Neuroprotective Mechanism for Alzheimer’s Disease

Background

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Neuroinflammation is a prevalent pathogenic stress leading to neuronal death in AD. Targeting neuroinflammation to keep neurons alive is an attractive strategy for AD therapy. 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) is a potent and blood-brain barrier permeable inhibitor of soluble epoxide hydrolase (sEH). It has a good efficacy on a wide range of chronic inflammatory diseases in preclinical animal models. However, the anti-neuroinflammatory effects and molecular mechanisms of TPPU for potential AD interventions remain elusive.

Technology Overview

Researchers at the University of Hawaii’s Molecular Biosciences and Bioengineering Department have developed a novel method using TPPU to treat AD.

TPPU selectively inhibits both sEH and p38β kinase, showing a neuropharmacology in multiple AD signaling pathways. TPPU effectively prevents neuronal death by mitigating amyloid toxicity, tau hyperphosphorylation and mitochondrial dysfunction in the human neuron SH-SY5Y cells, and promoting neurite outgrowth and suppressing activation and nuclear translocation of NF-κB for inflammatory responses.