There is considerable evidence that activated microglia play a central role in the pathogenesis of many prominent
neurodegenerative disorders, including Parkinson's and
Alzheimer's diseases. The elevated
NADPH oxidase activity of these microglia contributes importantly to their pathogenic impact, collaborating with increased iNOS activity to generate the cytotoxic
oxidant peroxynitrite.
Phycocyanobilin (PCB), a chromophore derived from
biliverdin that constitutes up to 1% of the dry weight of spirulina, has recently been shown to be a potent inhibitor of
NADPH oxidase. The possibility that orally administered PCB could reach the brain parenchyma in sufficient concentrations to influence microglial function is consistent with the findings of two rodent studies: orally administered
C-phycocyanin (the spirulina holoprotein that includes PCB) suppresses the neurotoxic impact of the
excitotoxin kainite in rats, and a diet high in spirulina ameliorates the loss of dopaminergic neurons in the
MPTP-induced
Parkinsonian syndrome in mice. Hence, supplemental PCB may have considerable potential for preventing or slowing the progression of a range of
neurodegenerative disorders. Some of the central physiological effects of PCB may also reflect inhibition of neuronal
NADPH oxidase, which is now known to have a modulatory impact on neuron function, and can mediate neurotoxicity in certain circumstances. Neuronal
NADPH oxidase activation is an obligate mediator of the central pressor effect of
angiotensin II, and there is suggestive evidence that it may also play a role in inflammatory
hyperalgesia; these findings point to possible
antihypertensive and
analgesic applications for PCB. The likely favorable effects of PCB on vascular health may also protect the brain by decreasing
stroke risk, and inhibition of
NADPH oxidase in rodents has been shown to lessen the neurotoxic impact of temporary
cerebral ischemia. PCB may thus have versatile potential for preserving the healthful function of the central nervous system into advanced old age--albeit optimal neuroprotection may require more complex regimens that incorporate PCB along with other well tolerated nutraceuticals and drugs, in conjunction with prudent lifestyle modifications.