Gut–Brain Axis: Potential Factors Involved in the Pathogenesis of Parkinson's Disease

Increasing evidence suggests an association between gastrointestinal (GI) disorders and susceptibility and progress of Parkinson's disease (PD). Gut–brain axis has been proposed to play important roles in the pathogenesis of PD, though the exact pathophysiologic mechanism has yet to be elucidated. Here, we discuss the common factors involved in both PD and GI disorders, including genes, altered gut microbiota, diet, environmental toxins, and altered mucosal immunity. Large-scale prospective clinical studies are needed to define the exact relationship between dietary factors, microbiome, and genetic factors in PD. Identification of early diagnostic markers and demonstration of the efficacy of diet modulation and regulation of gut microbiome through specific therapeutics can potentially change the treatment paradigm for PD.

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α-Synuclein TransgenicDrosophilaAs a Model of Parkinson's Disease and Related Synucleinopathies

Parkinson s Disease ◽

10.4061/2011/212706 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Hideya Mizuno ◽

Nobuhiro Fujikake ◽

Keiji Wada ◽

Yoshitaka Nagai

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Drosophila Melanogaster ◽

Large Scale ◽

Critical Role ◽

Lewy Bodies ◽

Transgenic Animals ◽

Increased Risk ◽

The Common ◽

Common Pathogenesis

α-Synuclein (α-Syn) is a major component of protein inclusions known as Lewy bodies, which are hallmarks of synucleinopathies such as Parkinson's disease (PD). Theα-Syn gene is one of the familial PD-causing genes and is also associated with an increased risk of sporadic PD. Numerous studies usingα-Syn expressing transgenic animals have indicated thatα-Syn plays a critical role in the common pathogenesis of synucleinopathies.Drosophila melanogasterhas several advantages for modeling human neurodegenerative diseases and is widely used for studying their pathomechanisms and therapies. In fact,Drosophilamodels expressingα-Syn have already been established and proven to replicate several features of human PD. In this paper, we review the current research on synucleinopathies usingα-SynDrosophilamodels and, moreover, explore the possibilities of these models for comprehensive genetic analyses and large-scale drug screening towards elucidating the molecular pathogenesis and developing therapies for synucleinopathies.

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Neuroinflammation in Parkinson’s Disease: Triggers, Mechanisms, and Immunotherapies

The Neuroscientist ◽

10.1177/1073858421991066 ◽

2021 ◽

pp. 107385842199106

Author(s):

Tai Wang ◽

Changhe Shi ◽

Haiyang Luo ◽

Huimin Zheng ◽

Liyuan Fan ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Genetic Factors ◽

Common Factor ◽

Feedback Loops ◽

Future Directions ◽

Immune Systems ◽

Key Issues ◽

The Common ◽

The Relationship

Parkinson’s disease (PD) is a heterogeneous neurodegenerative disease involving multiple etiologies and pathogenesis, in which neuroinflammation is a common factor. Both preclinical experiments and clinical studies provide evidence for the involvement of neuroinflammation in the pathophysiology of PD, although there are a number of key issues related to neuroinflammatory processes in PD that remain to be addressed. In this review, we highlight the relationship between the common pathological mechanisms of PD and neuroinflammation, including aggregation of α-synuclein, genetic factors, mitochondrial dysfunction, and gut microbiome dysbiosis. We also describe the two positive feedback loops initiated in PD after the immune system is activated, and their role in the pathogenesis of PD. In addition, the interconnections and differences between the central and peripheral immune systems are discussed. Finally, we review the latest progress in immunotherapy research for PD patients, and propose future directions for clinical research.

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The role of gut dysbiosis in Parkinson's disease: mechanistic insights andtherapeutic options

Brain ◽

10.1093/brain/awab156 ◽

2021 ◽

Author(s):

Qing Wang ◽

Yuqi Luo ◽

K Ray Chaudhuri ◽

Richard Reynolds ◽

Eng-King Tan ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Nervous System ◽

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Gastrointestinal Symptoms ◽

Fecal Microbiota ◽

Motor Symptoms ◽

Treatment Paradigm ◽

New Treatment

Abstract Parkinson's disease is a common neurodegenerative disease in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alteration in gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the central nervous system, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries and alterations of the gut microbiota in Parkinson's disease, and highlight current mechanistic insights on the microbiota-gut-brain axis in disease pathophysiology. We discuss the interactions between production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we also draw attention to diet modification, use of probiotics and prebiotics and fecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.

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