Nutraceuticals Targeting Generation and Oxidant Activity of Peroxynitrite May Aid Prevention and Control of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a chronic low-grade inflammatory process in which activated microglia generate cytotoxic factors—most prominently peroxynitrite—which induce the death and dysfunction of neighboring dopaminergic neurons. Dying neurons then release damage-associated molecular pattern proteins such as high mobility group box 1 which act on microglia via a range of receptors to amplify microglial activation. Since peroxynitrite is a key mediator in this process, it is proposed that nutraceutical measures which either suppress microglial production of peroxynitrite, or which promote the scavenging of peroxynitrite-derived oxidants, should have value for the prevention and control of PD. Peroxynitrite production can be quelled by suppressing activation of microglial NADPH oxidase—the source of its precursor superoxide—or by down-regulating the signaling pathways that promote microglial expression of inducible nitric oxide synthase (iNOS). Phycocyanobilin of spirulina, ferulic acid, long-chain omega-3 fatty acids, good vitamin D status, promotion of hydrogen sulfide production with taurine and N-acetylcysteine, caffeine, epigallocatechin-gallate, butyrogenic dietary fiber, and probiotics may have potential for blunting microglial iNOS induction. Scavenging of peroxynitrite-derived radicals may be amplified with supplemental zinc or inosine. Astaxanthin has potential for protecting the mitochondrial respiratory chain from peroxynitrite and environmental mitochondrial toxins. Healthful programs of nutraceutical supplementation may prove to be useful and feasible in the primary prevention or slow progression of pre-existing PD. Since damage to the mitochondria in dopaminergic neurons by environmental toxins is suspected to play a role in triggering the self-sustaining inflammation that drives PD pathogenesis, there is also reason to suspect that plant-based diets of modest protein content, and possibly a corn-rich diet high in spermidine, might provide protection from PD by boosting protective mitophagy and thereby aiding efficient mitochondrial function. Low-protein diets can also promote a more even response to levodopa therapy.

Heme Degradation in Pathophysiology of and Countermeasures to Inflammation-Associated Disease

“…Moreover, bilirubin possesses immunosuppressive/immunoregulatory properties, as demonstrated by both experimental and clinical studies [ 52 , 53 ]. It is also worth noting that phycocyyanobilin, an algal phytochemical with close structural homology to bilirubin, also exhibits potent antioxident and cytoprotective qualities, with potential for human clinical benefit [ 54 , 55 , 56 , 57 , 58 ].…”

“…In its native state, the compound is a component of the algal phycobiloproteins phycocyanin and allophycocyanin. Its close structural homology with bilirubin and negligible biological toxicity have made Spirulina an increasingly valuable dietary supplement for the maintenance of general health and both preventive medicine and therapy [ 54 , 55 , 56 , 57 , 58 ].…”

Mitochondrial DNA and Neurodegeneration: Any Role for Dietary Antioxidants?

“…Indeed, positive clinical outcomes exerted by antioxidants supplementation. For example, vitamins C [ 126 , 127 ], E [ 128 ] and N-acetylcysteine [ 129 ] have been demonstrated active in oxidative-stress related pathologies [ 130 , 131 ]. A large body of evidence shows that many dietary antioxidants can help to delay their onset and progression [ 6 , 132 , 133 , 134 ], in particular when applied at the early-stages of the disease, and the application of dietary antioxidants for the prevention of neurodegeneration has also been proposed [ 71 ].…”

Uso de probióticos em pacientes com doença de Parkinson: a importância do eixo intestino-cérebro e dietoterapia – uma revisão de literatura

“…Um dos outros processos inflamatórios crônicos da DP é quando a micróglia ativada gera fatores citotóxicos -principalmente o peroxinitrito -que induz a morte e a disfunção dos neurônios dopaminérgicos vizinhos (McCarty & Lerner, 2020). Os mesmos autores propuseram medidas nutracêuticas que suprem a produção microglial de peroxinitrito ou que promovam a eliminação de oxidantes derivados do peroxinitrito que ajuda para a prevenção e controle da DP.…”

“…Sugestões de ingestão suplementar adequada desses agentes. A possibilidade de que dietas à base de plantas com conteúdo modesto de proteínas possam ajudar na prevenção e controle da DP merecem atenção; essas dietas também são boas adjuvantes à terapia com levodopa (McCarty & Lerner, 2020). Em qualquer caso, é recomendável recomendar dietas à base de plantas, ricas em fibras e alimentos integrais, pois é esperado que eles forneçam proteção à saúde.…”