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The objective of the present study was to examine the role of selenium in the metabolism of Aβ and in Aβ-induced neuronal death. Selenium treatment significantly reduced Aβ40, Aβ42, and sAPPβ production by reducing Aβ producing β-secretase and γ-secretase activities. The lipid peroxidation product 4-Hydroxynonenal (HNE)-induced transcription of β-secretase (BACE1) was blocked by selenium. Finally, our data show that selenium protects against HNE and Aβ-mediated toxicity in primary cultured neurons. The present study suggests that selenium may be able to salvage the neuronal degeneration of Alzheimer's disease, thereby limiting β-amyloid production and neuronal death.

To investigate a potential molecular basis for a link between diabetes and atherosclerosis, experiments were performed to determine the role of NAD(P)H oxidase in the enhanced proliferative capacity of vascular smooth muscle cells (VSMC) from OLETF rat, an animal model of type 2 diabetes. An enhanced proliferative response to 10% fetal bovine serum with an increased cell cycle progression from G 1 to S phase as well as an augmented superoxide generation with an increased NAD(P)H oxidase activity were observed in diabetic versus control VSMC. Both the enhanced proliferation and superoxide generation in diabetic VSMC were significantly attenuated not only by diphenyleneiodonium (10 μM) and apocynin (100 μM), NAD(P)H oxidase inhibitors but also by protein tyrosine kinase inhibitors such as genistein (100 μM) and AG 112 (100 μM). Furthermore, the enhanced NAD(P)H oxidase activity in diabetic VSMC was significantly attenuated by genistein and AG112, but not by daidzein (100 μM), a genistein analogue devoid of protein tyrosine kinase inhibitory properties. Based on these results, it is suggested that the enhanced proliferative capacity of diabetic VSMC is closely related to the activation of NAD(P)H oxidase that is induced through activation of protein tyrosine kinase.