scholarly journals Inflammatory Response Modulation by Vitamin C in an MPTP Mouse Model of Parkinson’s Disease

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1155
Author(s):  
Francesco De Nuccio ◽  
Antonia Cianciulli ◽  
Chiara Porro ◽  
Marianna Kashyrina ◽  
Melania Ruggiero ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Vitamin C ◽  
Neurodegenerative Diseases ◽  
Cell Activation ◽  
Defense Mechanism ◽  
Inflammatory Responses ◽  
Anti Inflammatory ◽  
The Brain ◽  
Vit C

Vitamin C (Vit C) is anutrient present in many foods, particularly citrus fruits, green vegetables, tomatoes, and potatoes. Vit C is studied for its applications in the prevention and management of different pathologies, including neurodegenerative diseases. Neuroinflammation is a defense mechanism activated by a stimulus or an insult that is aimed at the preservation of the brain by promoting tissue repair and removing cellular debris; however, persistent inflammatory responses are detrimental and may lead to the pathogenesis and progression of neurodegenerative diseases like Parkinson’s disease (PD) and Alzheimer’s disease. PD is one of the most common chronic progressive neurodegenerative disorders, and oxidative stress is one of the most important factors involved in its pathogenesis and progression.Due to this, research on antioxidant and anti-inflammatory compounds is an important target for counteracting neurodegenerative diseases, including PD. In the central nervous system, the presence of Vit C in the brain is higher than in other body districts, but why and how this occurs is still unknown. In this research, Vit C, with its anti-inflammatory and anti-oxidative properties, is studied to better understand its contribution to brain protection; in particular, we have investigated the neuroprotective effects of Vit C in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of PD and its role in the modulation of neuroinflammation. First, we observed that Vit C significantly decreased the MPTP-induced loss of tyrosine hydroxylase (TH)-positive dopaminergic neuronal cells in the substantia nigra, as well as microglial cell activation and astrogliosis. Furthermore, gait and spontaneous locomotor activity, evaluated by an automated treadmill and the Open Field test, respectively, were partially ameliorated by Vit C treatment in MPTP-intoxicated animals. In relation to neuroinflammation, results show that Vit C reduced the protein and mRNA expression of inflammatory cytokines such as IL-6, TLR4, TNF-α, iNOS, and CD40, while anti-inflammatory proteins such as IL-10, CD163, TGF-β, and IL-4 increased. Interestingly, we show for the first time that Vit C reduces neuroinflammation by modulating microglial polarization and astrocyte activation. Moreover, Vit C was able to reduce NLRP3 activation, which is linked to the pathogenesis of many inflammatory diseases, including neuroinflammatory disorders. In conclusion, our study provides evidence that Vit C may represent a new promising dietary supplement for the prevention and alleviation of the inflammatory cascade of PD, thus contributing to neuroprotection.

scholarly journals Investigating the convergent mechanisms between Major Depressive Disorder and Parkinson’s disease

2020 ◽  
Author(s):  
Angela A Tran ◽  
Myra De Smet ◽  
Gary D. Grant ◽  
Tien K. Khoo ◽  
Dean L Pountney
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Cell Activation ◽  
Glutamate Excitotoxicity ◽  
Major Depressive ◽  
Glial Cell Activation ◽  
Underlying Mechanisms ◽  
The Brain

Major depressive disorder (MDD) affects more than cognition, having a temporal relationship with neuroinflammatory pathways of Parkinson’s disease (PD). Although this association is supported by epidemiological and clinical studies, the underlying mechanisms are unclear. Microglia and astrocytes play crucial roles in the pathophysiology of both MDD and PD. In PD, these cells can be activated by misfolded forms of the protein α-synuclein to release cytokines that can interact with multiple different physiological processes to produce depressive symptoms, including monoamine transport and availability, the hypothalamus-pituitary axis, and neurogenesis. In MDD, glial cell activation can be induced by peripheral inflammatory agents that cross the blood brain barrier and/or c-Fos signaling from neurons. The resulting neuroinflammation can cause neurodegeneration due to oxidative stress and glutamate excitotoxicity, contributing to PD pathology. Astrocytes are another major link due to their recognised role in the glymphatic clearance mechanism. Research suggesting that MDD causes astrocytic destruction or structural atrophy highlight the possibility that accumulation of α-synuclein in the brain is facilitated as the brain cannot adequately clear the protein aggregates. This review examines research into the overlapping pathophysiology of MDD and PD with particular focus on the roles of glial cells and neuroinflammation.

scholarly journals Soluble Epoxide Hydrolase Inhibition to Face Neuroinflammation in Parkinson’s Disease: A New Therapeutic Strategy

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 703 ◽  
Author(s):  
Mercè Pallàs ◽  
Santiago Vázquez ◽  
Coral Sanfeliu ◽  
Carles Galdeano ◽  
Christian Griñán-Ferré
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Epoxide Hydrolase ◽  
Active Role ◽  
Soluble Epoxide Hydrolase ◽  
Hydrolytic Activity ◽  
Neurodegenerative Process ◽  
Anti Inflammatory

Neuroinflammation is a crucial process associated with the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). Several pieces of evidence suggest an active role of lipid mediators, especially epoxy-fatty acids (EpFAs), in the genesis and control of neuroinflammation; 14,15-epoxyeicosatrienoic acid (14,15-EET) is one of the most commonly studied EpFAs, with anti-inflammatory properties. Soluble epoxide hydrolase (sEH) is implicated in the hydrolysis of 14,15-EET to its corresponding diol, which lacks anti-inflammatory properties. Preventing EET degradation thus increases its concentration in the brain through sEH inhibition, which represents a novel pharmacological approach to foster the reduction of neuroinflammation and by end neurodegeneration. Recently, it has been shown that sEH levels increase in brains of PD patients. Moreover, the pharmacological inhibition of the hydrolase domain of the enzyme or the use of sEH knockout mice reduced the deleterious effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. This paper overviews the knowledge of sEH and EETs in PD and the importance of blocking its hydrolytic activity, degrading EETs in PD physiopathology. We focus on imperative neuroinflammation participation in the neurodegenerative process in PD and the putative therapeutic role for sEH inhibitors. In this review, we also describe highlights in the general knowledge of the role of sEH in the central nervous system (CNS) and its participation in neurodegeneration. We conclude that sEH is one of the most promising therapeutic strategies for PD and other neurodegenerative diseases with chronic inflammation process, providing new insights into the crucial role of sEH in PD pathophysiology as well as a singular opportunity for drug development.

scholarly journals Cellular and Molecular Mediators of Neuroinflammation in the Pathogenesis of Parkinson’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Sandeep Vasant More ◽  
Hemant Kumar ◽  
In Su Kim ◽  
Soo-Yeol Song ◽  
Dong-Kug Choi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Defense Mechanism ◽  
Neuronal Degeneration ◽  
Neuronal Damage ◽  
Normal Structure ◽  
Host Defense Mechanism ◽  
And Function ◽  
The Relationship ◽  
The Brain

Neuroinflammation is a host-defense mechanism associated with restoration of normal structure and function of the brain and neutralization of an insult. Increasing neuropathological and biochemical evidence from the brains of individuals with Parkinson’s disease (PD) provides strong evidence for activation of neuroinflammatory pathways. Microglia, the resident innate immune cells, may play a major role in the inflammatory process of the diseased brain of patients with PD. Although microglia forms the first line of defense for the neural parenchyma, uncontrolled activation of microglia may directly affect neurons by releasing various molecular mediators such as inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β), nitric oxide, prostaglandin E2, and reactive oxygen and nitrogen species. Moreover, recent studies have reported that activated microglia phagocytose not only damaged cell debris but also intact neighboring cells. This phenomenon further supports their active participation in self-enduring neuronal damage cycles. As the relationship between PD and neuroinflammation is being studied, there is a realization that both cellular and molecular mediators are most likely assisting pathological processes leading to disease progression. Here, we discuss mediators of neuroinflammation, which are known activators released from damaged parenchyma of the brain and result in neuronal degeneration in patients with PD.

scholarly journals Clinicotherapeutic Potential of Leptin in Alzheimer’s Disease and Parkinson’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Soumyabrata Munshi ◽  
Vineet Kumar Khemka ◽  
Kalpita Banerjee ◽  
Sasanka Chakrabarti
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Peptide Hormone ◽  
The Elderly ◽  
Clinical Associations ◽  
The Brain

Chronic neurodegenerative diseases are a group of devastating neurological disorders that result in significant morbidity and mortality in the elderly population worldwide. Recent researches have shown some interesting associations of the classical antiobesity hormone leptin with two most important neurodegenerative diseases—Alzheimer’s disease (AD) and Parkinson’s disease (PD). Although several clinical studies have found the procognitive and memory-enhancing role of this peptide hormone in leptin-deficient patients, surprisingly it has not been used in any clinical trials involving patients with developing or full-blown neurodegenerative conditions. This review article is an attempt to bring together the existing information about the clinical associations of leptin with AD and PD. It starts with the basic understanding of leptin action in the brain and its derangements in these diseases and eventually discusses the potential of this hormone as a neuroprotective agent in clinical scenario.

scholarly journals LRRK2 in peripheral and central nervous system innate immunity: its link to Parkinson's disease

2017 ◽  
Vol 45 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Heyne Lee ◽  
William S. James ◽  
Sally A. Cowley
Keyword(s):  
Parkinson’S Disease ◽  
Central Nervous System ◽  
Parkinson's Disease ◽  
Innate Immunity ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Cell Activation ◽  
Physiological Function ◽  
Leucine Rich Repeat ◽  
Lrrk2 Gene

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are found in familial and idiopathic cases of Parkinson's disease (PD), but are also associated with immune-related disorders, notably Crohn's disease and leprosy. Although the physiological function of LRRK2 protein remains largely elusive, increasing evidence suggests that it plays a role in innate immunity, a process that also has been implicated in neurodegenerative diseases, including PD. Innate immunity involves macrophages and microglia, in which endogenous LRRK2 expression is precisely regulated and expression is strongly up-regulated upon cell activation. This brief report discusses the current understanding of the involvement of LRRK2 in innate immunity particularly in relation to PD, critically examining its role in myeloid cells, particularly macrophages and microglia.

scholarly journals Link between periodontal inflammatory disease and Parkinson’s disease: Case reports

2020 ◽  
Vol 5 (2) ◽  
pp. 084-088
Author(s):  
Ivan Minić ◽  
Ana Pejčić ◽  
Sanja Popović
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Oral Cavity ◽  
Inflammatory Responses ◽  
Case Reports ◽  
Nerve Cells ◽  
Entire Body ◽  
Health Maintenance ◽  
Disease Case ◽  
The Brain

Parkinson's disease (PD) is caused by a loss of nerve cells in the part of the brain called the substantianigra. Nerve cells in this part of the brain are responsible for producing a chemical called dopamine. The symptoms of Parkinson's disease usually only start to develop when around 80% of the nerve cells in the substantianigra have been lost. Uncontrolled severe periodontitis caused by periodontal pathogens represents a major infectious threat to the entire body, since released toxins and other inflammatory mediators can reach and affect distant organs. Until now, periodontal disease and Parkinson's disease has been linked only on the basis of poor motor and cognitive control in Parkinson's patient which leads to poor oral health maintenance. Evidence now suggests that chronic neuroinflammation is consistently associated with the pathophysiology of Parkinson's disease. Also, recently, systemic inflammation has been suggested as one of the contributing factors for neurodegeneration. The local inflammatory responses at the site of infection are often linked to CNS disorders such as Parkinson's disease. Infections in the oral cavity, untreated conditions, foci can contribute to the worsening of Parkinson's disease. It is concluded that it is necessary to repair the oral cavity in all patients in order to achieve possible improvement, and on the other hand in these patients it is necessary to fully rehabilitate the oral cavity due to daily functions of the oral cavity which are difficult due to the clinical condition.

scholarly journals Hypothalamic Neuropeptide Brain Protection: Focus on Oxytocin

2020 ◽  
Vol 9 (5) ◽  
pp. 1534
Author(s):  
Maria Antonietta Panaro ◽  
Tarek Benameur ◽  
Chiara Porro
Keyword(s):  
Neurodegenerative Diseases ◽  
Inflammatory Responses ◽  
Active Form ◽  
Neuroprotective Effects ◽  
Positive Effects ◽  
New Therapeutic Approaches ◽  
Cytokines And Chemokines ◽  
Anti Inflammatory ◽  
Milk Ejection Reflex ◽  
The Brain

Oxytocin (OXT) is hypothalamic neuropeptide synthetized in the brain by magnocellular and parvo cellular neurons of the paraventricular (PVN), supraoptic (SON) and accessory nuclei (AN) of the hypothalamus. OXT acts in the central and peripheral nervous systems via G-protein-coupled receptors. The classical physiological functions of OXT are uterine contractions, the milk ejection reflex during lactation, penile erection and sexual arousal, but recent studies have demonstrated that OXT may have anti-inflammatory and anti-oxidant properties and regulate immune and anti-inflammatory responses. In the pathogenesis of various neurodegenerative diseases, microglia are present in an active form and release high levels of pro-inflammatory cytokines and chemokines that are implicated in the process of neural injury. A promising treatment for neurodegenerative diseases involves new therapeutic approaches targeting activated microglia. Recent studies have reported that OXT exerts neuroprotective effects through the inhibition of production of pro-inflammatory mediators, and in the development of correct neural circuitry. The focus of this review is to attribute a new important role of OXT in neuroprotection through the microglia–OXT interaction of immature and adult brains. In addition, we analyzed the strategies that could enhance the delivery of OXT in the brain and amplify its positive effects.

scholarly journals Anti-Inflammatory Effects of the Novel Barbiturate Derivative MHY2699 in an MPTP-Induced Mouse Model of Parkinson’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1855
Author(s):  
Seulah Lee ◽  
Yeon Ji Suh ◽  
Yujeong Lee ◽  
Seonguk Yang ◽  
Dong Geun Hong ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Cell Activation ◽  
Motor Dysfunction ◽  
Dopamine Neurons ◽  
Neuroprotective Effects ◽  
Glial Cell Activation ◽  
Anti Inflammatory ◽  
Neuroprotective Treatment

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, and is caused by the death of dopamine neurons and neuroinflammation in the striatum and substantia nigra. Furthermore, the inflammatory response in PD is closely related to glial cell activation. This study examined the neuroprotective effects of the barbiturate derivative, MHY2699 [5-(4-hydroxy 3,5-dimethoxybenzyl)-2 thioxodihydropyrimidine-4,6(1H,5H)-dione] in a mouse model of PD. MHY2699 ameliorated MPP⁺-induced astrocyte activation and ROS production in primary astrocytes and inhibited the MPP⁺-induced phosphorylation of MAPK and NF-κB. The anti-inflammatory effects of MHY2699 in protecting neurons were examined in an MPTP-induced mouse model of PD. MHY2699 inhibited MPTP-induced motor dysfunction and prevented dopaminergic neuronal death, suggesting that it attenuated neuroinflammation. Overall, MHY2699 has potential as a neuroprotective treatment for PD.

Interlink Between Insulin Resistance and Neurodegeneration with an Update on Current Therapeutic Approaches

2020 ◽  
Vol 19 (3) ◽  
pp. 174-183
Author(s):  
Subrat Kumar Bhattamisra ◽  
Lee Yuen Shin ◽  
Hanis Izzati Binti Mohd Saad ◽  
Vikram Rao ◽  
Mayuren Candasamy ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Insulin Signaling ◽  
Therapeutic Approaches ◽  
The Brain

The interlink between diabetes mellitus and neurodegenerative diseases such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) has been identified by several researchers. Patients with Type-2 Diabetes Mellitus (T2DM) are found to be affected with cognitive impairments leading to learning and memory deficit, while patients with Type-1 Diabetes Mellitus (T1DM) showed less severe levels of these impairments in the brain. This review aimed to discuss the connection between insulin with the pathophysiology of neurodegenerative diseases (AD and PD) and the current therapeutic approached mediated through insulin for management of neurodegenerative diseases. An extensive literature search was conducted using keywords “insulin”; “insulin resistance”; “Alzheimer’s disease”; “Parkinson’s disease” in public domains of Google scholar, PubMed, and ScienceDirect. Selected articles were used to construct this review. Studies have shown that impaired insulin signaling contributes to the accumulation of amyloid-β, neurofibrillary tangles, tau proteins and α-synuclein in the brain. Whereas, improvement in insulin signaling slows down the progression of cognitive decline. Various therapeutic approaches for altering the insulin function in the brain have been researched. Besides intranasal insulin, other therapeutics like PPAR-γ agonists, neurotrophins, stem cell therapy and insulin-like growth factor-1 are under investigation. Research has shown that insulin insensitivity in T2DM leads to neurodegeneration through mechanisms involving a variety of extracellular, membrane receptor, and intracellular signaling pathway disruptions. Some therapeutics, such as intranasal administration of insulin and neuroactive substances have shown promise but face problems related to genetic background, accessibility to the brain, and invasiveness of the procedures.

Gene expression analysis in modeling Parkinson’s disease

2020 ◽  
pp. 103-104
Author(s):  
М.М. Руденок ◽  
А.Х. Алиева ◽  
А.А. Колачева ◽  
М.В. Угрюмов ◽  
П.А. Сломинский ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Systemic Disease ◽  
Molecular Genetic ◽  
Presymptomatic Stage ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome ◽  
The Brain ◽  
Transcriptome Level

Несмотря на очевидный прогресс, достигнутый в изучении молекулярно-генетических факторов и механизмов патогенеза болезни Паркинсона (БП), в настоящее время стало ясно, что нарушения в структуре ДНК не описывают весь спектр патологических изменений, наблюдаемых при развитии заболевания. В настоящее время показано, что существенное влияние на патогенез БП могут оказывать изменения на уровне транскриптома. В работе были использованы мышиные модели досимптомной стадии БП, поздней досимптомной и ранней симптомной (РСС) стадиями БП. Для полнотранскриптомного анализа пулов РНК тканей черной субстанции и стриатума мозга мышей использовались микрочипы MouseRef-8 v2.0 Expression BeadChip Kit («Illumina», США). Полученные данные указывают на последовательное вовлечение транскриптома в патогенез БП, а также на то, что изменения на транскриптомном уровне процессов транспорта и митохондриального биогенеза могут играть важную роль в нейродегенерации при БП уже на самых ранних этапах. Parkinson’s disease (PD) is a complex systemic disease, mainly associated with the death of dopaminergic neurons. Despite the obvious progress made in the study of molecular genetic factors and mechanisms of PD pathogenesis, it has now become clear that violations in the DNA structure do not describe the entire spectrum of pathological changes observed during the development of the disease. It has now been shown that changes at the transcriptome level can have a significant effect on the pathogenesis of PD. The authors used models of the presymptomatic stage of PD with mice decapitation after 6 hours (6 h-PSS), presymptomatic stage with decapitation after 24 hours (24 h-PSS), advanced presymptomatic (Adv-PSS) and early symptomatic (ESS) stages of PD. For whole transcriptome analysis of RNA pools of the substantia nigra and mouse striatum, the MouseRef-8 v2.0 Expression BeadChip Kit microchips (Illumina, USA) were used. As a result of the analysis of whole transcriptome data, it was shown that, there are a greater number of statistically significant changes in the tissues of the brain and peripheral blood of mice with Adv-PSS and ESS models of PD compared to 6 h-PSS and 24 h-PSS models. In general, the obtained data indicate the sequential involvement of the transcriptome in the pathogenesis of PD, as well as the fact that changes at the transcriptome level of the processes of transport and mitochondrial biogenesis can play an important role in neurodegeneration in PD at an early stage.

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