ABSTRACT
Microglia-driven neuroinflammation plays an important role in the development of Alzheimer's disease. Microglia activation is accompanied by the formation and chronic expression of TLR4 inflammarafts, defined as enlarged and cholesterol-rich lipid rafts serving as an assembly platform for TLR4 dimers and complexes of other inflammatory receptors. The secreted apoA-I binding protein (APOA1BP or AIBP) binds TLR4 and selectively targets cholesterol depletion machinery to TLR4 inflammaraft-expressing inflammatory, but not homeostatic microglia. Here we demonstrated that amyloid-beta (Aß) induced formation of TLR4 inflammarafts in microglia in vitro and in the brain of APP/PS1 mice. Mitochondria in Apoa1bp-/- APP/PS1 microglia were hyperbranched and cupped, which was accompanied by increased reactive oxygen species and the dilated endoplasmic reticulum. The size and number of Aß plaques and neuronal cell death were significantly increased, and the animal survival was decreased in Apoa1bp-/-APP/PS1 compared to APP/PS1 female mice. These results suggest that AIBP exerts control of TLR4 inflammarafts and mitochondrial dynamics in microglia and plays a protective role in Alzheimer's disease associated oxidative stress and neurodegeneration.
Subject(s)
Alzheimer Disease , Mitochondria , Phosphoproteins , Racemases and Epimerases , Toll-Like Receptor 4 , Animals , Female , Humans , Mice , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Alzheimer Disease/genetics , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Disease Models, Animal , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Microglia/metabolism , Microglia/pathology , Mitochondria/metabolism , Mitochondria/pathology , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Racemases and Epimerases/genetics , Phosphoproteins/geneticsABSTRACT
Microglia-driven neuroinflammation plays an important role in the development of Alzheimer's disease (AD). Microglia activation is accompanied by the formation and chronic maintenance of TLR4 inflammarafts, defined as enlarged and cholesterol-rich lipid rafts serving as an assembly platform for TLR4 dimers and complexes of other inflammatory receptors. The secreted apoA-I binding protein (APOA1BP or AIBP) binds TLR4 and selectively targets cholesterol depletion machinery to TLR4 inflammaraft expressing inflammatory, but not homeostatic microglia. Here we demonstrated that amyloid-beta (Aß) induced formation of TLR4 inflammarafts in microglia in vitro and in the brain of APP/PS1 mice. Mitochondria in Apoa1bp-/- APP/PS1 microglia were hyperbranched and cupped, which was accompanied by increased ROS and the dilated ER. The size and number of Aß plaques and neuronal cell death were significantly increased, and the animal survival was decreased in Apoa1bp-/- APP/PS1 compared to APP/PS1 female mice. These results suggest that AIBP exerts control of TLR4 inflammarafts and mitochondrial dynamics in microglia and plays a protective role in AD associated oxidative stress and neurodegeneration.
ABSTRACT
Guidelines for dietary recommendations and nutritional therapy for patients with inflammatory bowel disease (IBD) are lacking, and patients are moving toward popular defined diets for relief of symptoms and inflammation. However, many proposed diets involve elimination of specific foods or food groups and may exacerbate or inadequately replete micronutrient deficiencies that are prevalent in patients with IBD at baseline. Further, limited data are available to guide clinicians on the use of dietary protocols for IBD. This article reviews dietary risk factors for IBD and common beliefs about diet among patients with IBD, and how these aspects may inform general dietary recommendations for this patient population. Additionally, this article reviews dietary interventions used in the management of active IBD, with a focus on whole food diet-based therapies rather than enteral or parenteral nutrition, as well as their nutritional adequacy. This article also highlights various dietary concepts and approaches among patients with IBD, along with the potential for nutritional inadequacy of popular defined diets for IBD. Partnerships with registered dietitians are needed to guide patients with IBD in nutrition and dietary intervention. Larger randomized studies are needed to support evidence-based dietary recommendations for IBD.