Overnutrition Determines LPS Regulation of Mycotoxin Induced Neurotoxicity in Neurodegenerative Diseases

Abstract

Chronic neurodegenerative diseases are now associated with obesity and diabetes and linked to the developing and developed world. Interests in healthy diets have escalated that may prevent neurodegenerative diseases such as Parkinson's and Alzheimer's disease. The global metabolic syndrome involves lipoprotein abnormalities and insulin resistance and is the major disorder for induction of neurological disease. The effects of bacterial lipopolysaccharides (LPS) on dyslipidemia and NAFLD indicate that the clearance and metabolism of fungal mycotoxins are linked to hypercholesterolemia and amyloid beta oligomers. LPS and mycotoxins are associated with membrane lipid disturbances with effects on cholesterol interacting proteins, lipoprotein metabolism, and membrane apo E/amyloid beta interactions relevant to hypercholesterolemia with close connections to neurological diseases. The influence of diet on mycotoxin metabolism has accelerated with the close association between mycotoxin contamination from agricultural products such as apple juice, grains, alcohol, and coffee. Cholesterol efflux in lipoproteins and membrane cholesterol are determined by LPS with involvement of mycotoxin on amyloid beta metabolism. Nutritional interventions such as diets low in fat/carbohydrate/cholesterol have become of interest with relevance to low absorption of lipophilic LPS and mycotoxin into lipoproteins with rapid metabolism of mycotoxin to the liver with the prevention of neurodegeneration.

Keywords: Alzheimer’s disease; amyloid beta; apolipoprotein E; brain; cholesterol; dyslipidemia; insulin resistance; lipopolysaccarides; liver; mycotoxin.

Figure 1

Links between diet and neurodegeneration has escalated with the involvement of bacterial lipopolysaccarides and fungal mycotoxins in amyloid beta (Aβ) homeostasis. Nutrition and food science with diets that promote the low absorption of lipophilic LPS and mycotoxin into lipoproteins with the rapid hepatic metabolism of LPS/mycotoxins to the liver, have become important to prevent early neurotoxicity and to promote the survival of neurons with age.

Figure 2

Bacterial LPS and mycotoxin promote dyslipidemia, electrostatic Aβ oligomer formation via post translational or post transcriptional modifications. (1) Bacterial LPS and mycotoxin induce dyslipidemia and NAFLD; (2) LPS and mycotoxin alter cell and membrane cholesterol homeostasis with increased Aβ formation; (3) Defective Sirtuin 1 (Sirt 1) post transcriptional regulation and post-translational modifications of cholesterol interacting proteins by LPS/mycotoxin neutralize apo E and increase Aβ oligomerization with connections to insulin resistance and AD; (4) Electrostatic Aβ oligomer formation may be independent of the early neuron apoptosis associated with neurotoxicity in individuals with insulin resistance and neurodegenerative diseases (Parkinson’s disease and Alzheimer’s disease).