HDAC6 and hyperinsulinemic hypoglycemia, familial, 4: Western blotting analyses revealed that p62 intracellular levels were markedly higher in 3Tg-iAstro, compared with WT-iAstro, suggesting an altered autophagic flux in AD, possibly due to both an increased p62 synthesis and a decreased p62 proteolysis as indicated by the enhanced Nrf2 and the decreased HDAC6 intracellular levels in 3Tg-iAstro (Fig. 2D), in agreement with studies showing that p62 synthesis can be induced by an increase in Nrf2 expression upon UPS deficiency.