Figure 5: Potential biological mechanism behind the hypovitaminosis D-PD relationship.1,25(OH)2D) can down-regulate the expression of inducible nitric oxide synthase (iNOS). Therefore it follows that hypovitaminosis D may lead to more nitric oxide (NO) being produced due to an increase in iNOS. NO is able to react with superoxide anion (O2-) to form peroxynitrite (ONOO-), which is capable of causing harm to cells (not shown), generating additional RNS (not shown), and inhibiting the activity of glutathione reductase, an enzyme that regenerates glutathione from its oxidised form (GSSG). Thus, less of the anti-oxidant glutathione will be present with an increase of peroxynitrite. Cell damage and neurodegeneration may then proceed; this suggests a vicious cycle in which the death of neurons leads to microglial activation, which in turn potentiates neuronal damage.
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