Appetite Regulation and the Peripheral Sink Amyloid beta Clearance Pathway in Diabetes and Alzheimer’s Disease

Major interests in senescence and neurodegenerative diseases have raised concerns with relevance to appetite regulation and the inactivation of the peripheral sink amyloid beta (Aβ) clearance pathway. Appetite control is now critical to neuron survival with the peripheral sink Aβ clearance pathway and epigenetic alterations linked to neurodegeneration. The release of Aβ (MWT 4 kd) monomers from neurons is associated with the Aβ clearance from the brain and determined by the apolipoprotein E mediated efflux of Aβ across the blood brain barrier to the periphery with rapid uptake by the liver. The activation of the peripheral sink amyloid beta clearance pathway to reduce brain Aβ levels has been studied by various laboratories. Cellular senescence and toxic Aβ aggregation in diabetes and neurodegenerative diseases have become of major concern with the recent discovery of the Sirtuin 1 (Sirt 1) gene that is now the major gene involved in senescence and global chronic disease in man. Dietary interventions are now critical to appetite regulation and senescence with high calorie diets, bacterial lipopolysaccharides low zinc levels, mycotoxins and low magnesium levels associated with Sirt 1 repression and pro¬grammed cell death.