Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegener-ative disorder characterized by the loss of dopaminergic neurons in the substantia nigra parscompacta, leading to motor symptoms such as tremor, rigidity, and bradykinesia. The patho-logical hallmarks of PD include Lewy bodies and mechanisms like oxidative/nitrosativestress, chronic inflammation, and mitochondrial dysfunction. Nitric oxide (NO), pro-duced by nitric oxide synthase (NOS) isoforms, plays a dual role in neuroprotection andneurodegeneration. Excessive NO production exacerbates neuroinflammation and oxida-tive/nitrosative damage, contributing to dopaminergic cell death. This review exploresNO’s role in PD pathogenesis and investigates dietary nitrate as a therapeutic strategy toregulate NO levels. Methods: A literature review of studies addressing the role of NO inPD was conducted using major scientific databases, including PubMed, Scopus, and Webof Science, using keywords such as “nitric oxide”, “NOSs”, “Parkinson’s disease”, and“nitrate neuroprotection in PD”. Studies on nitrate metabolism via the nitrate–nitrite–NOpathway and its effects on PD hallmarks were analyzed. Studies regarding the role ofnitrosamine formation in PD, which are mainly formed during the nitrification processof amines (nitrogen-containing compounds), often due to chemical reactions in the pres-ence of nitrite or nitrate, were also examined. In particular, nitrate has been shown toinduce oxidative stress, affect the mitochondrial function, and contribute to inflammatoryphenomena in the brain, another factor closely related to the pathogenesis of PD. Results:Excessive NO production, particularly from iNOS and nNOS, was strongly associated withneuroinflammation and oxidative/nitrosative stress, amplifying neuronal damage in PD.Dietary nitrate was shown to enhance NO bioavailability through the nitrate–nitrite–NOpathway, mitigating inflammation and oxidative/nitrosative damage. Conclusions: Dys-regulated NO production contributes significantly to PD progression via inflammatoryand oxidative/nitrosative pathways. Dietary nitrate, by modulating NO levels, offersa promising therapeutic strategy to counteract these pathological mechanisms. Furtherclinical trials are warranted to establish its efficacy and optimize its use in PD management. (PDF) 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. Available from: https://www.researchgate.net/publication/388272442_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 [accessed Jan 22 2025].
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
GIANLUCA TRIPODI;Mauro Lombardo;Gilda Aiello;SARA BALDELLI
2025-01-01
Abstract
Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegener-ative disorder characterized by the loss of dopaminergic neurons in the substantia nigra parscompacta, leading to motor symptoms such as tremor, rigidity, and bradykinesia. The patho-logical hallmarks of PD include Lewy bodies and mechanisms like oxidative/nitrosativestress, chronic inflammation, and mitochondrial dysfunction. Nitric oxide (NO), pro-duced by nitric oxide synthase (NOS) isoforms, plays a dual role in neuroprotection andneurodegeneration. Excessive NO production exacerbates neuroinflammation and oxida-tive/nitrosative damage, contributing to dopaminergic cell death. This review exploresNO’s role in PD pathogenesis and investigates dietary nitrate as a therapeutic strategy toregulate NO levels. Methods: A literature review of studies addressing the role of NO inPD was conducted using major scientific databases, including PubMed, Scopus, and Webof Science, using keywords such as “nitric oxide”, “NOSs”, “Parkinson’s disease”, and“nitrate neuroprotection in PD”. Studies on nitrate metabolism via the nitrate–nitrite–NOpathway and its effects on PD hallmarks were analyzed. Studies regarding the role ofnitrosamine formation in PD, which are mainly formed during the nitrification processof amines (nitrogen-containing compounds), often due to chemical reactions in the pres-ence of nitrite or nitrate, were also examined. In particular, nitrate has been shown toinduce oxidative stress, affect the mitochondrial function, and contribute to inflammatoryphenomena in the brain, another factor closely related to the pathogenesis of PD. Results:Excessive NO production, particularly from iNOS and nNOS, was strongly associated withneuroinflammation and oxidative/nitrosative stress, amplifying neuronal damage in PD.Dietary nitrate was shown to enhance NO bioavailability through the nitrate–nitrite–NOpathway, mitigating inflammation and oxidative/nitrosative damage. Conclusions: Dys-regulated NO production contributes significantly to PD progression via inflammatoryand oxidative/nitrosative pathways. Dietary nitrate, by modulating NO levels, offersa promising therapeutic strategy to counteract these pathological mechanisms. Furtherclinical trials are warranted to establish its efficacy and optimize its use in PD management. (PDF) 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. Available from: https://www.researchgate.net/publication/388272442_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 [accessed Jan 22 2025].I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
