Abstract: The p62 protein has been analyzed and identified as the significant contributor to several metabolic pathways that lead to metabolic syndrome, Alzheimer's Disease, and other related diseases. The absence of the p62 protein has a profound effect on the accumulation of tau protein, amyloid beta protein and an increase in blood insulin levels. The accumulation of tau protein and amyloid beta protein in neurological tissues is a hallmark of neurological metabolic diseases such as Alzheimer's Disease and related dementias. Moreover, increase blood insulin levels is an indicator of insulin resistance in mammals. Accordingly, the present invention provides a method for screening a mammal for metabolic disease comprising the step of detecting the absence of the p62 protein.

Abstract: Methods and compositions for modulating the formation of intracellular aggregates are provided, in particular TRAF6 mediated intracellular aggregate formation. Additionally, methods and compositions for identifying modulators of intracellular aggregate formation are provided, for example methods for identifying compositions that inhibit or reduce the formation of intracellular aggregate formation.