Neuronal nitric oxide synthase phosphorylation induced by docosahexaenoic acid protects dopaminergic neurons in an experimental model of Parkinson’s disease

Parlak, Hande; Özkan, Ayşe; Dilmaç, Sayra; Tanrıöver, Gamze; Özsoy, Özlem; Ağar, Ayşel

doi:10.5603/fhc.a2018.0005

Cited by 10 publications

(22 citation statements)

References 54 publications

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“…Likewise, the omega-3 PUFA DHA protects DA neurons against MPTP–[69,70,71], paraquat—[72] or rotenone-induced toxicity [73] in rodent models and against effects of 6-OHDA-treatment in Caenorhabditis elegans , mice and rats [74,75,76], also when administered as TAG-DHA [77]. Moreover, DHA plays a crucial role in the differentiation of induced pluripotent stem cells (iPSCs) into functional DA neurons [78] and DHA supplementation protects DA neurons from the SN in MPTP-treated mice [79]. EPA and ethyl-EPA attenuate 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in SH-SY5Y cells, primary mesencephalic neurons, and brain slices [80,81], and in vivo reduce MPTP/probecenid-induced dyskinesia and memory deficits (without preventing nigrostriatal DA loss) [82].…”

Section: Fatty Acylsmentioning

confidence: 99%

The Role of Lipids in Parkinson’s Disease

Xicoy

Wieringa

Martens

2019

Cells

188

161

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Parkinson’s disease (PD) is a neurodegenerative disease characterized by a progressive loss of dopaminergic neurons from the nigrostriatal pathway, formation of Lewy bodies, and microgliosis. During the past decades multiple cellular pathways have been associated with PD pathology (i.e., oxidative stress, endosomal-lysosomal dysfunction, endoplasmic reticulum stress, and immune response), yet disease-modifying treatments are not available. We have recently used genetic data from familial and sporadic cases in an unbiased approach to build a molecular landscape for PD, revealing lipids as central players in this disease. Here we extensively review the current knowledge concerning the involvement of various subclasses of fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and lipoproteins in PD pathogenesis. Our review corroborates a central role for most lipid classes, but the available information is fragmented, not always reproducible, and sometimes differs by sex, age or PD etiology of the patients. This hinders drawing firm conclusions about causal or associative effects of dietary lipids or defects in specific steps of lipid metabolism in PD. Future technological advances in lipidomics and additional systematic studies on lipid species from PD patient material may improve this situation and lead to a better appreciation of the significance of lipids for this devastating disease.

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Section: Fatty Acylsmentioning

confidence: 99%

The Role of Lipids in Parkinson’s Disease

Xicoy

Wieringa

Martens

2019

Cells

188

161

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“…nNOS inhibition by N w nitro-L-arginine methyl ester can reduce NO accumulation in human induced pluripotent stem cell (hiPSC)derived PD neurons (harboring the A53T-SNCA mutation) protecting neurons from mitochondrial dysfunction 61 and rescuing axodendritic pathology 128 . Likewise, treatment with docosahexaenoic acid causes the phosphorylation of nNOS that in turn decreases nNOS activity preventing PD-like motor deficits in MPTP treatment in mice 15 . While inhibiting NOS may seem to be an obvious therapy, this is complicated by the fact that nitric oxide is integral for physiological function, particularly for the vascular system.…”

Section: Targeting Rns As a Pd Therapy Reducing Rns By Targeting Nosmentioning

confidence: 99%

“…For example, the phosphorylation of Ser847 is inhibitory, while de-phosphorylation of Ser847 stimulates nNOS activity 14 . Perhaps it is not surprising that docosahexaenoic acid, a supplement that phosphorylates nNOS (i.e., inhibits nNOS activity) protects dopaminergic neurons from MPTP toxicity in rodent models of PD 15 . In addition, while a number of nNOS interacting proteins have been identified, HSP90 (heat-shock protein 90) has been demonstrated to be an important regulator of protein homeostasis and plays a specific role in preventing aSyn aggregation 16 ascribing it significance in PD.…”

mentioning

confidence: 99%

Nitrosative stress in Parkinson’s disease

Stykel

Ryan

2022

npj Parkinsons Dis.

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Parkinson’s Disease (PD) is a neurodegenerative disorder characterized, in part, by the loss of dopaminergic neurons within the nigral-striatal pathway. Multiple lines of evidence support a role for reactive nitrogen species (RNS) in degeneration of this pathway, specifically nitric oxide (NO). This review will focus on how RNS leads to loss of dopaminergic neurons in PD and whether RNS accumulation represents a central signal in the degenerative cascade. Herein, we provide an overview of how RNS accumulates in PD by considering the various cellular sources of RNS including nNOS, iNOS, nitrate, and nitrite reduction and describe evidence that these sources are upregulating RNS in PD. We document that over 1/3 of the proteins that deposit in Lewy Bodies, are post-translationally modified (S-nitrosylated) by RNS and provide a broad description of how this elicits deleterious effects in neurons. In doing so, we identify specific proteins that are modified by RNS in neurons which are implicated in PD pathogenesis, with an emphasis on exacerbation of synucleinopathy. How nitration of alpha-synuclein (aSyn) leads to aSyn misfolding and toxicity in PD models is outlined. Furthermore, we delineate how RNS modulates known PD-related phenotypes including axo-dendritic-, mitochondrial-, and dopamine-dysfunctions. Finally, we discuss successful outcomes of therapeutics that target S-nitrosylation of proteins in Parkinson’s Disease related clinical trials. In conclusion, we argue that targeting RNS may be of therapeutic benefit for people in early clinical stages of PD.

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“…Because of richness in ω-3 fatty acids, such as eicosapentaenoic and docosahexaenoic acids, fish oil showed neuroprotective effects via multiple mechanisms. In MPTP-challenged mice, docosahexaenoic acid administration improved motor activity, reducing apoptosis of dopaminergic neurons and enhancing antioxidant defense ( Parlak et al., 2018 ). The beneficial effects of ω-3 were confirmed in a double-blind randomizedclinical trial: 12-week supplementation with ω-3 and vitamin E in PD patients reduced inflammatory and oxidative biomarkers and limited metabolic impairment associated with PD ( Taghizadeh et al., 2017 ).…”

Section: Nutraceutical Impact On Pd Pathogenic Mechanismsmentioning

confidence: 99%

Nutraceuticals: An integrative approach to starve Parkinson’s disease

Lama

Pirozzi

Avagliano

et al. 2020

Brain, Behavior, & Immunity - Health

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The therapeutic approach of multifactorial complex diseases is always a challenge; Parkinson’s disease (PD) is a heterogeneous neurodegenerative disorder triggered by genetic and environmental factors, contributing to its etiology. Indeed, several pathogenic mechanisms lead to selective dopaminergic neuronal injury, including oxidative stress, mitochondrial dysfunction, alteration of endoplasmic reticulum-to-Golgi protein trafficking, excitotoxicity, and neuroinflammation. Current treatment approaches include mainly dopamine replacement therapy or optimizing dopaminergic transmission; however, these strategies that do not counteract the pathogenic mechanisms underlying PD symptoms and often are less effective over time. Recently, there has been growing interest in the therapeutic use of nutraceuticals, that could represent an integrative approach to the pharmacological standard therapy and specifically affect one or more pathogenic pathways. The intake of nutraceuticals or nutritional modifications are generally safe and can be combined with current common drug therapy in most cases to improve the patient’s quality of life and/or mitigate PD symptoms. The current review focuses on several key nutritional compounds and dietary modifications that are effective on several pathogenic pathways involved in PD onset and progression, and further highlights the rationale behind their potential use for the prevention and treatment of PD.

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Neuronal nitric oxide synthase phosphorylation induced by docosahexaenoic acid protects dopaminergic neurons in an experimental model of Parkinson’s disease

Cited by 10 publications

References 54 publications

The Role of Lipids in Parkinson’s Disease

The Role of Lipids in Parkinson’s Disease

Nitrosative stress in Parkinson’s disease

Nutraceuticals: An integrative approach to starve Parkinson’s disease

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