scholarly journals Minireview on the Relations between Gut Microflora and Parkinson’s Disease: Further Biochemical (Oxidative Stress), Inflammatory, and Neurological Particularities

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Ovidiu-Dumitru Ilie ◽  
Alin Ciobica ◽  
Jack McKenna ◽  
Bogdan Doroftei ◽  
Ioannis Mavroudis
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gastrointestinal Tract ◽  
Gastrointestinal Symptoms ◽  
Progressive Increase ◽  
Signalling Pathways ◽  
Gut Microflora ◽  
Number Of Patients ◽  
The Brain

The aetiology of Parkinson’s disease (PD) is a highly debated topic. Despite the progressive increase in the number of patients diagnosed with PD over the last couple of decades, the causes remain largely unknown. This report is aimed at highlighting the main features of the microbial communities which have been termed “the second brain” that may be a major participant in the etiopathophysiology of PD. It is possible that dysbiosis could be caused by an overactivity of proinflammatory cytokines which act on the gastrointestinal tract as well as infections. The majority of patients who are diagnosed with PD display gastrointestinal symptoms as one of the earliest features. In addition, an unbalanced cycle of oxidative stress caused by dysbacteriosis may have the effect of gradually promoting PD’s specific phenotype. Thus, it seems that bacteria possess the ability to manipulate the brain by initiating specific responses, defining their capability to configure the human body, with oxidative stress playing a pivotal role in preventing infections but also in activating related signalling pathways.

scholarly journals Gastrointestinal Dysfunction in Parkinson’s Disease

2021 ◽  
Vol 10 (3) ◽  
pp. 493
Author(s):  
Casper Skjærbæk ◽  
Karoline Knudsen ◽  
Jacob Horsager ◽  
Per Borghammer
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gastrointestinal Tract ◽  
Gastrointestinal Symptoms ◽  
Gastrointestinal Pathology ◽  
Wide Range ◽  
Patients Experience ◽  
Progressive Accumulation ◽  
Non Motor Symptoms ◽  
The Brain

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Patients show deposits of pathological, aggregated α-synuclein not only in the brain but throughout almost the entire length of the digestive tract. This gives rise to non-motor symptoms particularly within the gastrointestinal tract and patients experience a wide range of frequent and burdensome symptoms such as dysphagia, bloating, and constipation. Recent evidence suggests that progressive accumulation of gastrointestinal pathology is underway several years before a clinical diagnosis of PD. Notably, constipation has been shown to increase the risk of developing PD and in contrast, truncal vagotomy seems to decrease the risk of PD. Animal models have demonstrated gut-to-brain spreading of pathological α-synuclein and it is currently being intensely studied whether PD begins in the gut of some patients. Gastrointestinal symptoms in PD have been investigated by the use of several different questionnaires. However, there is limited correspondence between subjective gastrointestinal symptoms and objective dysfunction along the gastrointestinal tract, and often the magnitude of dysfunction is underestimated by the use of questionnaires. Therefore, objective measures are important tools to clarify the degree of dysfunction in future studies of PD. Here, we summarize the types and prevalence of subjective gastrointestinal symptoms and objective dysfunction in PD. The potential importance of the gastrointestinal tract in the etiopathogenesis of PD is briefly discussed.

scholarly journals Frequency of non-motor symptoms in Peruvian patients with Parkinson's disease

2013 ◽  
Vol 71 (4) ◽  
pp. 216-219 ◽  
Author(s):  
Carlos Cosentino ◽  
Yesenia Nuñez ◽  
Luis Torres
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Progressive Increase ◽  
Motor Symptoms ◽  
Number Of Patients ◽  
Progression Of Disease ◽  
The Mean ◽  
Relationship Of ◽  
The Relationship ◽  
Non Motor Symptoms

Introduction: Non-motor symptoms in Parkinson's disease are often not well recognized in clinical practice. Non-motor symptoms questionnaire (NMSQuest) is a simple instrument that allows patients or caregivers to report non-motor symptoms in a practical manner. Objective: We attempted to determine the prevalence of non-motor symptoms in three hundred Parkinson's disease outpatients. Results: The mean total non-motor symptoms was 12.41, ranging from 0 to 27 of a maximum of 30. At least one was present in 99.3% of patients. A progressive increase in mean total score was observed across each 5-year interval. Depression domain scored the most “positive” answers while urinary and anxiety /memory were secondly and thirdly most prevalent respectively. Conclusion: The large number of patients included in this study allowed evaluation of the occurrence of non-motor symptoms in early and advanced disease in addition to the relationship of these kinds of symptoms with progression of disease.

scholarly journals What Is the Evidence that Parkinson’s Disease Is a Prion Disorder, Which Originates in the Gut?

2018 ◽  
Vol 19 (11) ◽  
pp. 3573 ◽  
Author(s):  
Małgorzata Kujawska ◽  
Jadwiga Jodynis-Liebert
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Neurodegenerative Disorder ◽  
Human Subjects ◽  
Gastrointestinal Symptoms ◽  
Convincing Evidence ◽  
Substantia Nigra Pars Compacta ◽  
Motor Nucleus ◽  
The Brain

Parkinson’s disease (PD) is a neurodegenerative disorder resulting from degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). PD is characterized by motor dysfunctions as well as gastrointestinal symptoms and mental impairment. The pathological hallmark of PD is an accumulation of misfolded α-synuclein aggregates within the brain. The etiology of PD and related synucleinopathy is poorly understood, but recently, the hypothesis that α-synuclein pathology spreads in a prion-like fashion originating in the gut has gained much scientific attention. A crucial clue was the appearance of constipation before the onset of motor symptoms, gut dysbiosis and synucleinopathy in PD patients. Another line of evidence, demonstrating accumulation of α-synuclein within the peripheral autonomic nervous system (PANS), including the enteric nervous system (ENS), and the dorsal motor nucleus of the vagus (DMV) support the concept that α-synuclein can spread from the ENS to the brain by the vagus nerve. The decreased risk of PD following truncal vagotomy supports this. The convincing evidence of the prion-like behavior of α-synuclein came from postmortem observations that pathological α-synuclein inclusions appeared in healthy grafted neurons. In this review, we summarize the available data from human subjects’ research and animal experiments, which seem to be the most suggestive for explaining the hypotheses.

scholarly journals Anti-inflammatory and Anti-oxidant Activity of Hidrox® in Rotenone-Induced Parkinson’s Disease in Mice

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 824 ◽  
Author(s):  
Rosalba Siracusa ◽  
Maria Scuto ◽  
Roberta Fusco ◽  
Angela Trovato ◽  
Maria Laura Ontario ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Human Life ◽  
Developed Countries ◽  
Progressive Increase ◽  
Behavioral Alterations ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Main Component

Background: In developed countries, the extension of human life is increasingly accompanied by a progressive increase in neurodegenerative diseases, most of which do not yet have effective therapy but only symptomatic treatments. In recent years, plant polyphenols have aroused considerable interest in the scientific community. The mechanisms currently hypothesized for the pathogenesis of Parkinson’s disease (PD) are neuroinflammation, oxidative stress and apoptosis. Hydroxytyrosol (HT), the main component of Hidrox® (HD), has been shown to have some of the highest free radical evacuation and anti-inflammatory activities. Here we wanted to study the role of HD on the neurobiological and behavioral alterations induced by rotenone. Methods: A study was conducted in which mice received HD (10 mg/kg, i.p.) concomitantly with rotenone (5 mg/kg, o.s.) for 28 days. Results: Locomotor activity, catalepsy, histological damage and several characteristic markers of the PD, such as the dopamine transporter (DAT) content, tyrosine hydroxylase (TH) and accumulation of α-synuclein, have been evaluated. Moreover, we observed the effects of HD on oxidative stress, neuroinflammation, apoptosis and inflammasomes. Taken together, the results obtained highlight HD’s ability to reduce the loss of dopaminergic neurons and the damage associated with it by counteracting the three main mechanisms of PD pathogenesis. Conclusion: HD is subject to fewer regulations than traditional drugs to improve patients’ brain health and could represent a promising nutraceutical choice to prevent PD.

scholarly journals N-Acetylcysteine Nanocarriers Protect against Oxidative Stress in a Cellular Model of Parkinson’s Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 600 ◽  
Author(s):  
Leah Mursaleen ◽  
Brendon Noble ◽  
Stefanie Ho Yi Chan ◽  
Satyanarayana Somavarapu ◽  
Mohammed Gulrez Zariwala
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Viability ◽  
Iron Status ◽  
Thiobarbituric Acid ◽  
Iron Chelator ◽  
Disease Modifying Therapy ◽  
First Time ◽  
The Brain

Oxidative stress is a key mediator in the development and progression of Parkinson’s disease (PD). The antioxidant N-acetylcysteine (NAC) has generated interest as a disease-modifying therapy for PD but is limited due to poor bioavailability, a short half-life, and limited access to the brain. The aim of this study was to formulate and utilise mitochondria-targeted nanocarriers for delivery of NAC alone and in combination with the iron chelator deferoxamine (DFO), and assess their ability to protect against oxidative stress in a cellular rotenone PD model. Pluronic F68 (P68) and dequalinium (DQA) nanocarriers were prepared by a modified thin-film hydration method. An MTT assay assessed cell viability and iron status was measured using a ferrozine assay and ferritin immunoassay. For oxidative stress, a modified cellular antioxidant activity assay and the thiobarbituric acid-reactive substances assay and mitochondrial hydroxyl assay were utilised. Overall, this study demonstrates, for the first time, successful formulation of NAC and NAC + DFO into P68 + DQA nanocarriers for neuronal delivery. The results indicate that NAC and NAC + DFO nanocarriers have the potential characteristics to access the brain and that 1000 μM P68 + DQA NAC exhibited the strongest ability to protect against reduced cell viability (p = 0.0001), increased iron (p = 0.0033) and oxidative stress (p ≤ 0.0003). These NAC nanocarriers therefore demonstrate significant potential to be transitioned for further preclinical testing for PD.

scholarly journals MICROBIOTA INTESTINAL RELACIONADA A DOENÇA DE PARKINSON

2021 ◽  
Vol 5 (1) ◽  
pp. 49-60
Author(s):  
Caroline Felix da Silva ◽  
Graziele Estevo Azevedo ◽  
Natália Franco Taketani
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gastrointestinal Tract ◽  
Intestinal Microbiota ◽  
Direct Relationship ◽  
Progressive Disease ◽  
Signs And Symptoms ◽  
The Body ◽  
Early Age ◽  
The Brain

RESUMO. A Doença de Parkinson é uma doença crônica, neurodegenerativa e progressiva onde não tem cura. Ainda há muitas investigações para se descobrir a causa da patologia. Em estudos recentes descobriram que pode ter uma relação direta com intestino, com a possibilidade de origem na microbiota intestinal e espalhando-se até o cérebro, com relação a uma desregulação no trato gastrointestinal. É reconhecido que, antes de aparecer os sinais e sintomas motores da doença, o organismo começa a sofrer alterações desde cedo, como a constipação intestinal, com o fortalecimento da hipótese de que a doença de Parkinson tenha início no trato gastrointestinal, e chegue até o cérebro através do nervo vago. Este trabalho pretende abordar sobre a microbiota intestinal e a sua conexão com a doença de Parkinson fazendo revisão de estudos e evidência de como sua composição no hospedeiro pode influenciar o seu metabolismo. A modulação da microbiota intestinal poderá, então, ser uma estratégia para o desenvolvimento de novas opções terapêuticas para o tratamento de doenças neurodegenerativas. ABSTRACT. Parkinson's Disease is a chronic, neurodegenerative and progressive disease that has no cure. There are still many investigations to discover the cause of the pathology. In recent studies they found that it may have a direct relationship with the intestine, with the possibility of originating in the intestinal microbiota and spreading to the brain, with respect to dysregulation in the gastrointestinal tract. It is recognized that, before the appearance of the motor signs and symptoms of the disease, the body begins to undergo changes from an early age, such as intestinal constipation, with the strengthening of the hypothesis that Parkinson's disease starts in the gastrointestinal tract and reaches the brain through the vagus nerve. This work intends to approach the intestinal microbiota and its connection with Parkinson's disease, reviewing studies and evidence on how its composition in the host can influence its metabolism. The modulation of the intestinal microbiota could then be a strategy for the development of new therapeutic options for the treatment of neurodegenerative diseases.

scholarly journals Epigenetic inactivation of the autophagy–lysosomal system in appendix in Parkinson’s disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Juozas Gordevicius ◽  
Peipei Li ◽  
Lee L. Marshall ◽  
Bryan A. Killinger ◽  
Sean Lang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Dna Methylation ◽  
Parkinson's Disease ◽  
Gastrointestinal Tract ◽  
Aberrant Methylation ◽  
Epigenetic Alterations ◽  
Potential Mechanism ◽  
Lysosomal System ◽  
A Site ◽  
The Brain

AbstractThe gastrointestinal tract may be a site of origin for α-synuclein pathology in idiopathic Parkinson’s disease (PD). Disruption of the autophagy-lysosome pathway (ALP) may contribute to α-synuclein aggregation. Here we examined epigenetic alterations in the ALP in the appendix by deep sequencing DNA methylation at 521 ALP genes. We identified aberrant methylation at 928 cytosines affecting 326 ALP genes in the appendix of individuals with PD and widespread hypermethylation that is also seen in the brain of individuals with PD. In mice, we find that DNA methylation changes at ALP genes induced by chronic gut inflammation are greatly exacerbated by α-synuclein pathology. DNA methylation changes at ALP genes induced by synucleinopathy are associated with the ALP abnormalities observed in the appendix of individuals with PD specifically involving lysosomal genes. Our work identifies epigenetic dysregulation of the ALP which may suggest a potential mechanism for accumulation of α-synuclein pathology in idiopathic PD.

scholarly journals Synthesis of Alginate-Curcumin Nanocomposite and Its Protective Role in Transgenic Drosophila Model of Parkinson’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yasir Hasan Siddique ◽  
Wasi Khan ◽  
Braj Raj Singh ◽  
Alim H. Naqvi
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Bodies ◽  
Protective Role ◽  
Alpha Synuclein ◽  
Lower Permeability ◽  
Normal Human ◽  
Climbing Ability ◽  
The Brain

The genetic models in Drosophila provide a platform to understand the mechanism associated with degenerative diseases. The model for Parkinson's disease (PD) based on normal human alpha-synuclein (αS) expression was used in the present study. The aggregation of αS in brain leads to the formation of Lewy bodies and selective loss of dopaminergic neurons due to oxidative stress. Polyphenols generally have the reduced oral bioavailability, increased metabolic turnover, and lower permeability through the blood brain barrier. In the present study, the effect of synthesized alginate-curcumin nanocomposite was studied on the climbing ability of the PD model flies, lipid peroxidation, and apoptosis in the brain of PD model flies. The alginate-curcumin nanocomposite at final doses of 10−5, 10−3, and 10−1 g/mL was supplemented with diet, and the flies were allowed to feed for 24 days. A significant dose-dependent delay in the loss of climbing ability and reduction in the oxidative stress and apoptosis in the brain of PD model flies were observed. The results suggest that alginate-curcumin nanocomposite is potent in delaying the climbing disability of PD model flies and also reduced the oxidative stress as well as apoptosis in the brain of PD model flies.

Sign in / Sign up

Export Citation Format

Share Document