scholarly journals Review: The Role of Intestinal Dysbiosis in Parkinson’s Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Yiying Huang ◽  
Jinchi Liao ◽  
Xu Liu ◽  
Yunxiao Zhong ◽  
Xiaodong Cai ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Microglial Activation ◽  
Molecular Mimicry ◽  
Clinical Symptoms ◽  
Gastrointestinal Microbiota ◽  
Barrier Failure ◽  
Intestinal Dysbiosis ◽  
And Oxidative Stress

Several studies have highlighted the roles played by the gut microbiome in central nervous system diseases. Clinical symptoms and neuropathology have suggested that Parkinson’s disease may originate in the gut, which is home to approximately 100 trillion microbes. Alterations in the gastrointestinal microbiota populations may promote the development and progression of Parkinson’s disease. Here, we reviewed existing studies that have explored the role of intestinal dysbiosis in Parkinson’s disease, focusing on the roles of microbiota, their metabolites, and components in inflammation, barrier failure, microglial activation, and α-synuclein pathology. We conclude that there are intestinal dysbiosis in Parkinson’s disease. Intestinal dysbiosis is likely involved in the pathogenesis of Parkinson’s disease through mechanisms that include barrier destruction, inflammation and oxidative stress, decreased dopamine production, and molecular mimicry. Additional studies remain necessary to explore and verify the mechanisms through which dysbiosis may cause or promote Parkinson’s disease. Preclinical studies have shown that gastrointestinal microbial therapy may represent an effective and novel treatment for Parkinson’s disease; however, more studies, especially clinical studies, are necessary to explore the curative effects of microbial therapy in Parkinson’s disease.

scholarly journals Peripheral aetiopathogenic drivers and mediators of Parkinson’s disease and co-morbidities: role of gastrointestinal microbiota

2015 ◽  
Vol 22 (1) ◽  
pp. 22-32 ◽  
Author(s):  
Sylvia M. Dobbs ◽  
R. John Dobbs ◽  
Clive Weller ◽  
André Charlett ◽  
Aisha Augustin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gastrointestinal Microbiota

scholarly journals The role of mitochondria-targeted antioxidant MitoQ in neurodegenerative disease

2018 ◽  
pp. 1-8
Author(s):  
Linlin Zhang ◽  
Aurelio Reyes ◽  
Xiangdong Wang
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disease ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
And Oxidative Stress

Abstract: The discovery of charged molecules being able to cross the mitochondrial membrane has prompted many scholars to exploit this idea to find a way of preventing or slowing down aging. In this paper, we will focus on mitochondriatargeted antioxidants, which are cationic derivatives of plastoquinone, and in particular on the mitochondria-targeted antioxidant therapy of neurodegenerative diseases. It is well known that the accumulation of amyloid-β peptide (Aβ) in mitochondria and its related mitochondrial dysfunction are critical signatures of Alzheimer’ s disease (AD). In another neurodegenerative disease, Parkinson’s disease (PD), the loss of dopaminergic neurons in the substantia nigra and the production of Lewy bodies are among their pathological features. Pathogenesis of Parkinson’s disease and Alzheimer’s disease has been frequently linked to mitochondrial dysfunction and oxidative stress. Recent studies show that MitoQ, a mitochondria-targeted antioxidant, may possess therapeutic potential for Aβ-related and oxidative stress-associated neurodegenerative diseases, especially AD. Although MitoQ has been developed to the stage of clinical trials in PD, its true clinical effect still need further verification. This review aims to discuss the role of mitochondrial pathology in neurodegenerative diseases, as well as the recent development of mitochondrial targeted antioxidants as a potential treatment for these diseases by removing excess oxygen free radicals and inhibiting lipid peroxidation in order to improve mitochondrial function.  

Role of Mitochondria and Oxidative Stress in Parkinson’s Disease

2014 ◽  
pp. 521-548
Author(s):  
Renato Santos ◽  
Sónia Correia ◽  
Susana Cardoso ◽  
Cristina Carvalho ◽  
Emanuel Candeias ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
And Oxidative Stress

scholarly journals Galectin-3 Deletion Reduces LPS and Acute Colitis-Induced Pro-Inflammatory Microglial Activation in the Ventral Mesencephalon

2021 ◽  
Vol 12 ◽  
Author(s):  
Ana M. Espinosa-Oliva ◽  
Pablo García-Miranda ◽  
Isabel María Alonso-Bellido ◽  
Ana E. Carvajal ◽  
Melania González-Rodríguez ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Microglial Activation ◽  
Peripheral Inflammation ◽  
Ventral Mesencephalon ◽  
Predisposing Factor ◽  
Promising Strategy ◽  
Microglia Polarization ◽  
Galectin 3

Parkinson’s disease is a highly prevalent neurological disorder for which there is currently no cure. Therefore, the knowledge of risk factors as well as the development of new putative molecular targets is mandatory. In this sense, peripheral inflammation, especially the originated in the colon, is emerging as a predisposing factor for suffering this disease. We have largely studied the pleiotropic roles of galectin-3 in driving microglia-associated immune responses. However, studies aimed at elucidating the role of galectin-3 in peripheral inflammation in terms of microglia polarization are lacking. To achieve this, we have evaluated the effect of galectin-3 deletion in two different models of acute peripheral inflammation: intraperitoneal injection of lipopolysaccharide or gut inflammation induced by oral administration of dextran sodium sulfate. We found that under peripheral inflammation the number of microglial cells and the expression levels of pro-inflammatory mediators take place specifically in the dopaminergic system, thus supporting causative links between Parkinson’s disease and peripheral inflammation. Absence of galectin-3 highly reduced neuroinflammation in both models, suggesting an important central regulatory role of galectin-3 in driving microglial activation provoked by the peripheral inflammation. Thus, modulation of galectin-3 function emerges as a promising strategy to minimize undesired microglia polarization states.

scholarly journals Circadian rhythms, Neuroinflammation and Oxidative Stress in the Story of Parkinson’s Disease

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 314 ◽  
Author(s):  
Alexandre Vallée ◽  
Yves Lecarpentier ◽  
Rémy Guillevin ◽  
Jean-Noël Vallée
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Circadian Rhythms ◽  
Substantia Nigra Pars Compacta ◽  
Main Risk Factor ◽  
Progressive Degeneration ◽  
Physiological Pathways ◽  
And Oxidative Stress

Parkinson’s disease (PD) is one of the main neurodegenerative disease characterized by a progressive degeneration of neurons constituted by dopamine in the substantia nigra pars compacta. The etiologies of PD remain unclear. Aging is the main risk factor for PD. Aging could dysregulate molecular pathways controlling cell homeostatic mechanisms. PD cells are the sites of several metabolic abnormalities including neuroinflammation and oxidative stress. Metabolic structures are driven by circadian rhythms. Biologic rhythms are complex systems interacting with the environment and controlling several physiological pathways. Recent findings have shown that the dysregulation of the circadian rhythms is correlated with PD and its metabolic dysregulations. This review is focused on the key role of circadian rhythms and their impact on neuroinflammation and oxidative stress in Parkinson’s disease.

scholarly journals The role of selected antioxidants in the development and treatment of Parkinson’s disease

2019 ◽  
Vol 73 ◽  
pp. 516-528
Author(s):  
Dominika Markowska ◽  
Daria Malicka ◽  
Jarosław Nuszkiewicz ◽  
Karolina Szewczyk-Golec
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Modern Medicine ◽  
Substantia Nigra Pars Compacta ◽  
Current State ◽  
And Oxidative Stress ◽  
Significant Health

The widespread aging of societies results in the intensification of the development of neurodegenerative diseases associated with advanced age, including Parkinson’s disease. Unfortunately, modern medicine is not able to unequivocally determine the etiopathogenesis of the disease, which is why no causative treatment can be given. According to the current state of knowledge, in the course of Parkinson’s disease the substantia nigra pars compacta in the midbrain degenerates, leading to a decrease in dopamine levels in the patient’s brain. This results in neurotransmission disturbances and the development of undesirable effects. Neurodegenerative changes are supposedly caused by the combination of various factors, including genetic factors, chronic inflammation, the interaction of toxins, disturbances in protein metabolism, and oxidative stress. The therapeutic possibilities associated with the administration of antioxidants, which could alleviate increased oxidative stress and contribute to the better quality of life of the patient, are considered. Taking into account the studies on numerous antioxidants, such as coenzyme Q10, B vitamins, vitamin D, vitamin E and resveratrol, it cannot be unequivocally stated that this is an effective treatment, because experiments carried out on both humans and animals gave conflicting results. It is reasonable to say that antioxidant deficiencies should be avoided and the physiological levels should be sought, as this may be translated into significant health benefits.

scholarly journals The role of mitochondria-targeted antioxidant MitoQ in neurodegenerative disease

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Linlin Zhang ◽  
Aurelio Reyes ◽  
Xiangdong Wang
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disease ◽  
And Oxidative Stress

The discovery of charged molecules being able to cross the mitochondrial membrane has prompted many scholars to exploit this idea to find a way of preventing or slowing down aging. In this paper, we will focus on mitochondria-targeted antioxidants, which are cationic derivatives of plastoquinone, and in particular on the mitochondria-targeted antioxidant therapy of neurodegenerative diseases. It is well known that the accumulation of amyloid-β peptide (Aβ) in mitochondria and its related mitochondrial dysfunction are critical signatures of Alzheimer’s disease (AD). In another neurodegenerative disease, Parkinson’s disease (PD), the loss of dopaminergic neurons in the substantia nigra and the production of Lewy bodies are among their pathological features. Pathogenesis of Parkinson’s disease and Alzheimer’s disease has been frequently linked to mitochondrial dysfunction and oxidative stress. Recent studies show that MitoQ, a mitochondria-targeted antioxidant, may possess therapeutic potential for Aβ-related and oxidative stress-associated neurodegenerative diseases, especially AD. Although MitoQ has been developed to the stage of clinical trials in PD, its true clinical effect still need further verification. This review aims to discuss the role of mitochondrial pathology in neurodegenerative diseases, as well as the recent development of mitochondrial targeted antioxidants as a potential treatment for these diseases by removing excess oxygen free radicals and inhibiting lipid peroxidation in order to improve mitochondrial function.

scholarly journals Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunna Li ◽  
Yun Xia ◽  
Sijia Yin ◽  
Fang Wan ◽  
Junjie Hu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Microglial Activation ◽  
Clinical Symptoms ◽  
Therapeutic Drugs ◽  
Chronic Neuroinflammation ◽  
Nf Kappab ◽  
Pro Inflammatory Cytokines

According to emerging studies, the excessive activation of microglia and the subsequent release of pro-inflammatory cytokines play important roles in the pathogenesis and progression of Parkinson’s disease (PD). However, the exact mechanisms governing chronic neuroinflammation remain elusive. Findings demonstrate an elevated level of NLRP3 inflammasome in activated microglia in the substantia nigra of PD patients. Activated NLRP3 inflammasome aggravates the pathology and accelerates the progression of neurodegenerative diseases. Abnormal protein aggregation of α-synuclein (α-syn), a pathologically relevant protein of PD, were reported to activate the NLRP3 inflammasome of microglia through interaction with toll-like receptors (TLRs). This eventually releases pro-inflammatory cytokines through the translocation of nuclear factor kappa-B (NF-κB) and causes an impairment of mitochondria, thus damaging the dopaminergic neurons. Currently, therapeutic drugs for PD are primarily aimed at providing relief from its clinical symptoms, and there are no well-established strategies to halt or reverse this disease. In this review, we aimed to update existing knowledge on the role of the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis and microglial activation in PD. In addition, this review summarizes recent progress on the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis of microglia as a potential target for PD treatment by inhibiting microglial activation.

scholarly journals Role of Mitogen Activated Protein Kinase Signaling in Parkinson’s Disease

2018 ◽  
Vol 19 (10) ◽  
pp. 2973 ◽  
Author(s):  
Anastasiia Bohush ◽  
Grazyna Niewiadomska ◽  
Anna Filipek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Map Kinases ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Important Player

Parkinson’s disease (PD) is a neurodegenerative disorder caused by insufficient dopamine production due to the loss of 50% to 70% of dopaminergic neurons. A shortage of dopamine, which is predominantly produced by the dopaminergic neurons within the substantia nigra, causes clinical symptoms such as reduction of muscle mass, impaired body balance, akinesia, bradykinesia, tremors, postural instability, etc. Lastly, this can lead to a total loss of physical movement and death. Since no cure for PD has been developed up to now, researchers using cell cultures and animal models focus their work on searching for potential therapeutic targets in order to develop effective treatments. In recent years, genetic studies have prominently advocated for the role of improper protein phosphorylation caused by a dysfunction in kinases and/or phosphatases as an important player in progression and pathogenesis of PD. Thus, in this review, we focus on the role of selected MAP kinases such as JNKs, ERK1/2, and p38 MAP kinases in PD pathology.

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