Cholecystokinin and glucagon-like peptide-1 analogues regulate intestinal tight junction, inflammation, dopaminergic neurons and α-synuclein accumulation in the colon of two Parkinson's disease mouse models

Su, Yunfang; Liu, Ningning; Zhang, Zijuan; Li, Hao; Ma, Junxia; Yuan, Ye; Shi, Ming; Liu, Jihong; Zhao, Zhang; Hölscher, Christian

doi:10.1016/j.ejphar.2022.175029

Cited by 15 publications

(10 citation statements)

References 41 publications

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“…Despite this, a study using a novel gut-to-brain α-syn transmission mice paradigm discovered that pathologic α-syn spread throughout the brain as indicated by phosphorylation of α-syn at serine-129. , The prevention of α-synucleinopathy progression from the stomach to the brain, along with neurodegeneration and behavioral impairments, was also demonstrated by truncal vagotomy and α-syn deficiency, supporting Braak’s theory . As a result DA in the DMN of the vagus nerve, SN, locus ceruleus, hippocampus, amygdala, and eventually the neocortex are thought to be the first CNS regions where aberrant α-syn deposition occurs . Many preclinical studies have shown that GM affect GBA, and the absence of normal GM in the intestine demonstrates the significant effects on the body by changing the various signaling pathways involved in the pathogenesis of PD and associated with neurochemical alterations, such as altered levels of brain-derived neurotrophic factor (BDNF) in the cortical and hippocampal regions, lowered levels of 5-hydroxytryptamine (5-HT) expression, raised monoamine levels, and decreased synaptic plasticity …”

Section: Various Signaling Pathways Involved In Propagation Of α-Syn ...mentioning

confidence: 99%

“…The rate at which α-syn spreads pathologically between cells is partially determined by the state of their lysosomes. Upon lysosomal degradation, released α-syn reaggregates to form the toxic LP structure, which is subsequently delivered to the synaptic terminals at the end of microtubule axons. − …”

Section: Various Signaling Pathways Involved In Propagation Of α-Syn ...mentioning

confidence: 99%

“…95 As a result DA in the DMN of the vagus nerve, SN, locus ceruleus, hippocampus, amygdala, and eventually the neocortex are thought to be the first CNS regions where aberrant α-syn deposition occurs. 96 Many preclinical studies have shown that GM affect GBA, and the absence of normal GM in the intestine demonstrates the significant effects on the body by changing the various signaling pathways involved in the pathogenesis of PD and associated with neurochemical alterations, such as altered levels of brain-derived neurotrophic factor (BDNF) in the cortical and hippocampal regions, lowered levels of 5hydroxytryptamine (5-HT) expression, raised monoamine levels, and decreased synaptic plasticity. 97 4.1.…”

Section: Various Signaling Pathways Involved In Propagation Of α-Syn ...mentioning

confidence: 99%

See 2 more Smart Citations

Comprehensive Review on Potential Signaling Pathways Involving the Transfer of α-Synuclein from the Gut to the Brain That Leads to Parkinson’s Disease

Kumari

Taliyan

Dubey

2023

ACS Chem. Neurosci.

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Parkinson’s disease is the second most prevalent neurological disease after Alzheimer’s. Primarily, old age males are more affected than females. The aggregates of oligomeric forms of α-synuclein cause the loss of dopaminergic neurons in the substantia nigra pars compacta. Further, it leads to dopamine shortage in the striatum region. According to recent preclinical studies, environmental factors like pesticides, food supplements, pathogens, etc. enter the body through the mouth or nose and ultimately reach the gut. Further, these factors get accumulated in enteric nervous system which leads to misfolding of α-synuclein gene, and aggregation of this gene results in Lewy pathology in the gut and reaches to the brain through the vagus nerve. This evidence showed a strong bidirectional connection between the gut and the brain, which leads to gastrointestinal problems in Parkinson patients. Moreover, several studies reveal that patients with Parkinson experience more gastrointestinal issues in the early stages of the disease, such as constipation, increased motility, gut inflammation, etc. This review article focuses on the transmission of α-synuclein and the mechanisms involved in the link between the gut and the brain in Parkinson’s disease. Also, this review explores the various pathways involved in Parkinson and current therapeutic approaches for the improvement of Parkinson’s disease.

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Section: Various Signaling Pathways Involved In Propagation Of α-Syn ...mentioning

confidence: 99%

Section: Various Signaling Pathways Involved In Propagation Of α-Syn ...mentioning

confidence: 99%

Section: Various Signaling Pathways Involved In Propagation Of α-Syn ...mentioning

confidence: 99%

See 1 more Smart Citation

Comprehensive Review on Potential Signaling Pathways Involving the Transfer of α-Synuclein from the Gut to the Brain That Leads to Parkinson’s Disease

Kumari

Taliyan

Dubey

2023

ACS Chem. Neurosci.

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“…Therapeutically, attempts to reduce systemic inflammation have been made by treating PD mice with analogues of the anti-inflammatory molecules cholecystokinin and glucagon-like peptide1. Results are promising, since reductions in tight junction leakage, colonic inflammation, gut α-synuclein aggregates and dopaminergic neural loss have been observed [ 151 ].…”

Section: Parkinson’s Disease and Gut Microbiota: Links And Mechanismsmentioning

confidence: 99%

The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

Varesi¹,

Campagnoli²,

Fahmideh³

et al. 2022

IJMS

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The bidirectional interaction between the gut microbiota (GM) and the Central Nervous System, the so-called gut microbiota brain axis (GMBA), deeply affects brain function and has an important impact on the development of neurodegenerative diseases. In Parkinson’s disease (PD), gastrointestinal symptoms often precede the onset of motor and non-motor manifestations, and alterations in the GM composition accompany disease pathogenesis. Several studies have been conducted to unravel the role of dysbiosis and intestinal permeability in PD onset and progression, but the therapeutic and diagnostic applications of GM modifying approaches remain to be fully elucidated. After a brief introduction on the involvement of GMBA in the disease, we present evidence for GM alterations and leaky gut in PD patients. According to these data, we then review the potential of GM-based signatures to serve as disease biomarkers and we highlight the emerging role of probiotics, prebiotics, antibiotics, dietary interventions, and fecal microbiota transplantation as supportive therapeutic approaches in PD. Finally, we analyze the mutual influence between commonly prescribed PD medications and gut-microbiota, and we offer insights on the involvement also of nasal and oral microbiota in PD pathology, thus providing a comprehensive and up-to-date overview on the role of microbial features in disease diagnosis and treatment.

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“…Consistent with this pathological model of PD, one clinical study found evidence of leaky gut indicated by: widespread inflammation and disrupted GI epithelial tissue; an increase in calprotectin as well as zonulin, two well-validated biochemical markers of gut inflammation and oxidative stress, in fecal matter and serum in more than 50% of PD cases [ 278 ]. Additionally, immunohistochemical data suggest that the integrity of the gut barrier is compromised in PD cases as evidenced by alterations in tight junctions in GI epithelia [ 279 ]. In PD cases, the expression of claudin, occludin, and occludens-1—three structural proteins that are involved in the assembly and maintenance of tight junctions—is aberrantly altered in the colon in PD cases and is associated with increased permeability of intestinal epithelial barriers [ 65 , 280 ].…”

Section: Human Neuroimmune Diseases With Altered Microbiomesmentioning

confidence: 99%

Mucosal Immunity and the Gut-Microbiota-Brain-Axis in Neuroimmune Disease

Sterling

Dodd

Alhamdi

et al. 2022

IJMS

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Recent advances in next-generation sequencing (NGS) technologies have opened the door to a wellspring of information regarding the composition of the gut microbiota. Leveraging NGS technology, early metagenomic studies revealed that several diseases, such as Alzheimer’s disease, Parkinson’s disease, autism, and myalgic encephalomyelitis, are characterized by alterations in the diversity of gut-associated microbes. More recently, interest has shifted toward understanding how these microbes impact their host, with a special emphasis on their interactions with the brain. Such interactions typically occur either systemically, through the production of small molecules in the gut that are released into circulation, or through signaling via the vagus nerves which directly connect the enteric nervous system to the central nervous system. Collectively, this system of communication is now commonly referred to as the gut-microbiota-brain axis. While equally important, little attention has focused on the causes of the alterations in the composition of gut microbiota. Although several factors can contribute, mucosal immunity plays a significant role in shaping the microbiota in both healthy individuals and in association with several diseases. The purpose of this review is to provide a brief overview of the components of mucosal immunity that impact the gut microbiota and then discuss how altered immunological conditions may shape the gut microbiota and consequently affect neuroimmune diseases, using a select group of common neuroimmune diseases as examples.

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Cholecystokinin and glucagon-like peptide-1 analogues regulate intestinal tight junction, inflammation, dopaminergic neurons and α-synuclein accumulation in the colon of two Parkinson's disease mouse models

Cited by 15 publications

References 41 publications

Comprehensive Review on Potential Signaling Pathways Involving the Transfer of α-Synuclein from the Gut to the Brain That Leads to Parkinson’s Disease

Comprehensive Review on Potential Signaling Pathways Involving the Transfer of α-Synuclein from the Gut to the Brain That Leads to Parkinson’s Disease

The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

Mucosal Immunity and the Gut-Microbiota-Brain-Axis in Neuroimmune Disease

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