Nitric Oxide in Parkinson's Disease: The Potential Role of Dietary Nitrate in Enhancing Cognitive and Motor Health via the Nitrate-Nitrite-Nitric Oxide Pathway.

Background/objectives: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the , leading to motor symptoms such as tremor, rigidity, and bradykinesia. The pathological hallmarks of PD include Lewy bodies and mechanisms like oxidative/nitrosative stress, chronic inflammation, and mitochondrial dysfunction. Nitric oxide (NO), produced by nitric oxide synthase (NOS) isoforms, plays a dual role in neuroprotection and neurodegeneration. Excessive NO production exacerbates neuroinflammation and oxidative/nitrosative damage, contributing to dopaminergic cell death. This review explores NO's role in PD pathogenesis and investigates dietary nitrate as a therapeutic strategy to regulate NO levels.

Methods: A literature review of studies addressing the role of NO in PD was conducted using major scientific databases, including PubMed, Scopus, and Web of Science, using keywords such as "nitric oxide", "NOSs", "Parkinson's disease", and "nitrate neuroprotection in PD". Studies on nitrate metabolism via the nitrate-nitrite-NO pathway and its effects on PD hallmarks were analyzed. Studies regarding the role of nitrosamine formation in PD, which are mainly formed during the nitrification process of amines (nitrogen-containing compounds), often due to chemical reactions in the presence of nitrite or nitrate, were also examined. In particular, nitrate has been shown to induce oxidative stress, affect the mitochondrial function, and contribute to inflammatory phenomena in the brain, another factor closely related to the pathogenesis of PD.

Results: Excessive NO production, particularly from iNOS and nNOS, was strongly associated with neuroinflammation and oxidative/nitrosative stress, amplifying neuronal damage in PD. Dietary nitrate was shown to enhance NO bioavailability through the nitrate-nitrite-NO pathway, mitigating inflammation and oxidative/nitrosative damage.

Conclusions: Dysregulated NO production contributes significantly to PD progression via inflammatory and oxidative/nitrosative pathways. Dietary nitrate, by modulating NO levels, offers a promising therapeutic strategy to counteract these pathological mechanisms. Further clinical trials are warranted to establish its efficacy and optimize its use in PD management.