Figure 13.

Proposed working models for Nosustrophine as an epinutraceutical bioproduct with therapeutic potential against AD. (A) The primary methyl donor for DNA and histone methylation reactions is SAM. DNMTs convert SAM into SAH. AHCY in Nosustrophine interacts with and increases the activity of DNMT1, promoting the conversion of SAM into SAH. SAH is subsequently hydrolyzed by AHCY into Hcy. AHCY also increases de novo DNA methylation via DNMT1 activation; global DNA hypomethylation facilitates AD pathogenesis. (B) NAMPT, a rate-limiting enzyme that catalyzes the first step in NAD+ production, was detected in Nosustrophine. NAMPT overexpression elevates NAD+ levels, which stimulate SIRT1 expression, increases cerebral blood flow and improves cognitive function in AD. The presence of NAMPT in Nosustrophine may account for the increase in SIRT1 expression in Nosustrophine-treated older (8–9-month-old) 3xTg-AD mice. 3xTg-AD, triple-transgenic mouse model of AD; AD, Alzheimer’s disease; AHCY, adenosylhomocysteinase; DNMT, DNA methyltransferase; Hcy, homocysteine; NAD+, nicotinamide adenine dinucleotide; NAMPT, nicotinamide phosphoribosyltransferase; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; SIRT1, Sirtuin 1.