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 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 Motor and Nonmotor Symptoms of Parkinson’s Disease: Antagonistic Pleiotropy Phenomena Derived from α-Synuclein Evolvability?

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Yoshiki Takamatsu ◽  
Masayo Fujita ◽  
Gilbert J. Ho ◽  
Ryoko Wada ◽  
Shuei Sugama ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Body ◽  
Gastrointestinal Symptoms ◽  
Lewy Bodies ◽  
Antagonistic Pleiotropy ◽  
Nonmotor Symptoms ◽  
Novel Therapy ◽  
Wide Range ◽  
Lewy Body Diseases

Lewy body diseases, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are associated with a wide range of nonmotor symptoms (NMS), including cognitive impairment, depression and anxiety, sleep disorders, gastrointestinal symptoms, and autonomic failure. The reason why such diverse and disabling NMS have not been weeded out but have persisted across evolution is unknown. As such, one possibility would be that the NMS might be somehow beneficial during development and/or reproductive stages, a possibility consistent with our recent view as to the evolvability of amyloidogenic proteins (APs) such as α-synuclein (αS) and amyloid-β (Aβ) in the brain. Based on the heterogeneity of protofibrillar AP forms in terms of structure and cytotoxicity, we recently proposed that APs might act as vehicles to deliver information regarding diverse internal and environmental stressors. Also, we defined evolvability to be an epigenetic phenomenon whereby APs are transgenerationally transmitted from parents to offspring to cope with future brain stressors in the offspring, likely benefitting the offspring. In this context, the main objective is to discuss whether NMS might be relevant to evolvability. According to this view, information regarding NMS may be transgenerationally transmitted by heterogeneous APs to offspring, preventing or attenuating the stresses related to such symptoms. On the other hand, NMS associated with Lewy body pathology might manifest through an aging-associated antagonistic pleiotropy mechanism. Given that NMS are not only specific to Lewy body diseases but also displayed in other disorders, including amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD), these conditions might share common mechanisms related to evolvability. This might give insight into novel therapy strategies based on antagonistic pleiotropy rather than on individual NMS from which to develop disease-modifying therapies.

scholarly journals Non-Coding RNAs in the Brain-Heart Axis: The Case of Parkinson’s Disease

2020 ◽  
Vol 21 (18) ◽  
pp. 6513 ◽  
Author(s):  
Shubhra Acharya ◽  
Antonio Salgado-Somoza ◽  
Francesca Maria Stefanizzi ◽  
Andrew I. Lumley ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Throughput ◽  
Regulatory Networks ◽  
Current Knowledge ◽  
Circular Rnas ◽  
Clinical Markers ◽  
Wide Range ◽  
Non Coding Rnas ◽  
The Brain

Parkinson’s disease (PD) is a complex and heterogeneous disorder involving multiple genetic and environmental influences. Although a wide range of PD risk factors and clinical markers for the symptomatic motor stage of the disease have been identified, there are still no reliable biomarkers available for the early pre-motor phase of PD and for predicting disease progression. High-throughput RNA-based biomarker profiling and modeling may provide a means to exploit the joint information content from a multitude of markers to derive diagnostic and prognostic signatures. In the field of PD biomarker research, currently, no clinically validated RNA-based biomarker models are available, but previous studies reported several significantly disease-associated changes in RNA abundances and activities in multiple human tissues and body fluids. Here, we review the current knowledge of the regulation and function of non-coding RNAs in PD, focusing on microRNAs, long non-coding RNAs, and circular RNAs. Since there is growing evidence for functional interactions between the heart and the brain, we discuss the benefits of studying the role of non-coding RNAs in organ interactions when deciphering the complex regulatory networks involved in PD progression. We finally review important concepts of harmonization and curation of high throughput datasets, and we discuss the potential of systems biomedicine to derive and evaluate RNA biomarker signatures from high-throughput expression data.

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 Dynamic changes in the CD163+ and CCR2+ peripheral monocytes during Parkinson’s disease

2021 ◽  
Author(s):  
Sara Konstantin Nissen ◽  
Kristine Farmen ◽  
Mikkel Carstensen ◽  
Claudia Schulte ◽  
David Goldeck ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dendritic Cells ◽  
Alpha Synuclein ◽  
Mononuclear Phagocytes ◽  
Motor Symptoms ◽  
Hla Dr ◽  
Non Motor Symptoms ◽  
The Brain ◽  
Classical Monocytes

AbstractBackgroundAlpha-synuclein aggregates and accumulation are associated with immune activation and neurodegeneration in Parkinson’s disease. The immune activation is not only dependent on the brain-resident microglial cells but also involves peripheral immune cells, such as mononuclear phagocytes including monocytes and dendritic cells, found in the blood as well as infiltrated into the brain. Understanding the involvement of the peripheral immune component in Parkinson’s disease is essential for the development of immunomodulatory treatment, which might modify disease progression. We aimed to study the profile of circulating mononuclear phagocytes in early- and late-stage Parkinson’s disease by analyzing surface-expressed molecules related to phagocytosis, alpha-synuclein sensing, and tissue-migration.MethodsMulti-color flow cytometry on peripheral mononuclear cells from cross-sectional samples of 80 gender-balance individuals with early- and late-stage sporadic Parkinson’s disease, and 29 controls, as well as longitudinal samples from seven patients and one control. Cells were delineated into natural killer cells, monocyte subtypes, and dendritic cells with cell frequencies and surface marker expressions compared between patients and controls, and correlated with standardized clinical motor and non-motor scores.ResultsOverall, we found elevated frequencies and surface levels of markers related to migration (CCR2, CD11b) and phagocytosis (CD163) particularly on the elevated classical and intermediate monocytes in patients with Parkinson’s disease for less than five years. This corresponded to a decrease of non-classical monocytes and dendritic cells. We observed an increased HLA-DR expression late in disease and sexual-dimorphism with TLR-4 expression decreased in women with PD but not in males. The disease-associated immune changes on TLR4, CCR2, and CD11b were correlated with non-motor symptoms such as olfaction or cognition. While many alterations were normalized at late disease stage, other changes remained, such as the increased HLA-DR and CD163 expressions.ConclusionsOur data highlight a role for peripheral CD163+ and migration-competent classical monocytes in Parkinson’s disease. The study further suggests that the peripheral immune system is dynamically altered in Parkinson’s disease stages and directly related to both non-motor symptoms and the sex-bias of the disease.

Drosophila melanogaster a versatile model of Parkinson’s Disease

2021 ◽  
Vol 20 ◽  
Author(s):  
Falaq Naz ◽  
Yasir Hasan Siddique
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drosophila Melanogaster ◽  
Lewy Bodies ◽  
Substantia Nigra Pars Compacta ◽  
Maintenance Cost ◽  
The Novel ◽  
Life Threatening ◽  
Non Motor Symptoms ◽  
The Brain

: Parkinson's Disease (PD) is one of the most prevalent, recurrent and life-threatening neurodegenerative disease. However, the precise mechanism underlying this disease is not yet clearly understood. For understanding the pathogenesis of PD, it is essential to identify the symptoms along with the novel biological markers and to develop strategies which could lead towards the development of effective therapy. PD is associated with Lewy bodies (LBs) formation and the loss of dopaminergic neurons in the substantia nigra pars compacta of mid brain region. For the improvement in treatment strategiesas well as understanding the pathophysiology of the PD in number ofanimal models have been introduced that can recapitulatethe pathophysiology, motor and non-motor symptoms of PD. In contrast to mammalian models like rodents, mice and monkey, Drosophila is easy to handle as well as it maintenance cost is low.Due to the anatomical differencesin the brain and other major organsof human and fly,the issues of standardizing the methods or experiments to analyze behavioral aspects (walking, writhing, eating and sleeping) are difficult in flies. Thepresent review highlights the studies carried out for PD since 2000, using Drosophila melanogaster.

scholarly journals Self-Reported Symptoms of Parkinson’s Disease by Sex and Disease Duration

2016 ◽  
Vol 39 (11) ◽  
pp. 1412-1428 ◽  
Author(s):  
Ju Young Shin ◽  
Ryan T. Pohlig ◽  
Barbara Habermann
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Duration ◽  
Community Dwelling ◽  
Motor Symptoms ◽  
Cross Sectional ◽  
Wide Range ◽  
Future Care ◽  
Descriptive Survey ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is a neurodegenerative disease with a wide range of symptom presentations. The purpose of this research was to compare self-reported motor and non-motor symptoms of PD by sex and disease duration. This study was a cross-sectional descriptive survey in community-dwelling people with PD. A total of 141 participants (64.6% response rate; 59.6% men; Mage = 69.7 years) were included. Males reported more rigidity, speech problems, sexual dysfunction, memory problems, and socializing problems than females. The number of motor symptoms in three groups divided by increments of 5 years was significantly increased. Postural instability, freezing, off periods, dyskinesia, speech problems, and hallucinations/psychosis were significantly increased as the disease duration increased. Thorough assessment of motor and non-motor symptoms could decrease the risk of inadequate symptom management. Provision of information regarding PD symptoms at each stage may help people with PD and their caregivers in planning their future care and life.

scholarly journals α-synuclein−lipoprotein interactions and elevated ApoE level in cerebrospinal fluid from Parkinson's disease patients

2019 ◽  
Vol 116 (30) ◽  
pp. 15226-15235 ◽  
Author(s):  
Wojciech Paslawski ◽  
Justyna Zareba-Paslawska ◽  
Xiaoqun Zhang ◽  
Katharina Hölzl ◽  
Henrik Wadensten ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Interacting Proteins ◽  
Extracellular Milieu ◽  
Progressive Accumulation ◽  
The Brain

The progressive accumulation, aggregation, and spread of α-synuclein (αSN) are common hallmarks of Parkinson’s disease (PD) pathology. Moreover, numerous proteins interact with αSN species, influencing its toxicity in the brain. In the present study, we extended analyses of αSN-interacting proteins to cerebrospinal fluid (CSF). Using coimmunoprecipitation, followed by mass spectrometry, we found that αSN colocalize with apolipoproteins on lipoprotein vesicles. We confirmed these interactions using several methods, including the enrichment of lipoproteins with a recombinant αSN, and the subsequent uptake of prepared vesicles by human dopaminergic neuronal-like cells. Further, we report an increased level of ApoE in CSF from early PD patients compared with matched controls in 3 independent cohorts. Moreover, in contrast to controls, we observed the presence of ApoE-positive neuromelanin-containing dopaminergic neurons in substantia nigra of PD patients. In conclusion, the cooccurrence of αSN on lipoprotein vesicles, and their uptake by dopaminergic neurons along with an increase of ApoE in early PD, proposes a mechanism(s) for αSN spreading in the extracellular milieu of 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 Clinical and pathophysiological aspects of non-motor manifestations of Parkinson's disease

2020 ◽  
Vol 18 (4) ◽  
pp. 222-232
Author(s):  
M. A. Nikitina ◽  
N. G. Zhukova ◽  
E. Yu. Bragina ◽  
V. M. Alifirova ◽  
I. A. Zhukova ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Picture ◽  
Motor Symptoms ◽  
Correct Treatment ◽  
Neurodegenerative Process ◽  
Wide Range ◽  
Anxiety Depression ◽  
Non Motor Symptoms

Non-motor symptoms are an essential manifestation of the clinical picture of Parkinson's disease (PD). This literature review is devoted to the study of recent advances in the field of clinical and pathophysiological aspects of the non-motor manifestations of Parkinson's disease.Aim. The aim was to study and generalize the wide range of non-motor manifestations of PD and their features in this pathology, and to reveal the pathophysiological link between motor and non-motor manifestations of the disease and the role of the neurodegenerative process in the clinical picture of PD.Materials and methods. Keywords (Parkinson's disease, non-motor symptoms, apathy, anxiety, depression, sleep disorder, pain) search in the Web of Science, Core Collection, Scopus, Pubmed databases.Results. Knowledge about the presence of PD non-motor symptoms, characteristics of their manifestations improve their diagnosis and help to choose the correct treatment strategy. This survey comprises nonmotor manifestations of PD, such as: mood disorders (apathy, anxiety, depression), impulse control disorders (dopamine disregulation syndrome), sleep disorders (insomnia, excessive daytime sleepiness, bouts of sleepiness, conduct disorder in REM phase of sleep), autonomic disorders (constipation, enuresis, thermoregulatory dysfunction, cardiovascular disorders, orthostatic hypotension), and cognitive impairment. 

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