Insights into Anti-Inflammatory Capabilities of Plant Polyphenols for Treatment of Alzheimer’s Disease

Principal Investigator: Melissa Moss, PhD

PubMed

The global aim of our research is to use biomedical engineering and molecular biology tools to study the mechanism responsible for changes in protein folding, cell-protein interaction and inflammatory immune response to misfolded proteins in Alzheimer’s Disease (AD). AD is characterized by deposits of aggregated amyloid-b protein (Ab) within the brain parenchyma and cerebrovasculature. This pathology is coupled with elevated inflammatory response. AD brains with Ab deposits co-localized with vessel-associated immune cells exhibit a compromised blood-brain barrier (BBB) integrity.

melissa Moss
Melissa Moss
Project PI:

The goal of the current study is to expand on our preliminary
results that

  1. Interaction of  soluble Ab aggregates, but not monomeric Ab with cerebrovascular endothelial cells is responsible for inflammatory responses such as increased endothelial expression of adhesion molecules, increased monocyte adhesion and reduced permeability when tested in in vitro cultures.
  2. These inflammatory responses by aggregated Ab are mediated via NF-kB signaling, where reactive oxygen species (ROS) induced by aggregated Ab serve as second messengers.

We will test the hypothesis that plant polyphenols will reduce Ab-induced inflammatory responses in endothelial cells by interfering with both Ab aggregation and ROS second messengers. We will test if plant polyphenols act as aggregation inhibitors to attenuate Ab-induced vascular inflammatory responses. Combinations of polyphenols that are synergistic in action as demonstrated by their ability to  reduce NF-kB signaling, exhibiting similar anti-oxidant capabilities and varying ability to inhibit Ab aggregation will be identified. These studies will form the basis for future therapeutics development for the treatment of Alzheimer’s disease using plant polyphenols.

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