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

Chao, Yin Xia; Gulam, Muhammad Yaaseen; Chia, Nicholas Shyh Jenn; Feng, Lei; Rötzschke, Olaf; Tan, Eng‐King

doi:10.3389/fneur.2020.00849

Cited by 22 publications

(26 citation statements)

References 68 publications

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“…New attention to the importance and function of the appendix proved that it has a significant role in the immune system of the gut, the microbiome, and the possibility of being a port of transfer of misfolded branched Asyn protein by a prion-like process through the vagus nerve to the brainstem then to be disseminated to the brain reaching different areas explaining the different clinical and pathological findings [8,10,13]. A significant laboratory and animal study supported this gut-brain axis hypothesis [12]. Truncal vagotomy may be associated with a lower incidence of PD [14].…”

Section: Introductionmentioning

confidence: 91%

“…Non-motor manifestations of PD like anosmia, constipation, depression, dementia, sleep disturbances, and other autonomic dysfunction suggest that PD is not restricted to SNpc, but rather a multisystem disease involving other parts of the central and peripheral nervous system [9]. The discovery of Asyn in the mucosa of the gastrointestinal tract [10,11], particularly in the vermiform appendix, proposes a possible link between the gut and the brain: the gut-brain axis [12]. New attention to the importance and function of the appendix proved that it has a significant role in the immune system of the gut, the microbiome, and the possibility of being a port of transfer of misfolded branched Asyn protein by a prion-like process through the vagus nerve to the brainstem then to be disseminated to the brain reaching different areas explaining the different clinical and pathological findings [8,10,13].…”

Section: Introductionmentioning

confidence: 99%

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The role of appendectomy in the development of Parkinson’s disease: a retrospective study in a teaching hospital in Jordan

Dahbour

Subuh

Haddad

et al. 2021

Egypt J Neurol Psychiatry Neurosurg

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Background Parkinson’s disease is a degenerative brain disease related to the accumulation of an abnormally aggregated alpha-synuclein protein. A hypothesis was presumed that this protein will be transported retrogradely from the gastrointestinal tract ultimately leading to the disease. Various epidemiologic studies have shown conflicting results. This study reports the prevalence of appendectomy in Jordanian parkinsonian patients and compares it to controls seen at one major teaching hospital in Jordan. This is a retrospective study of 266 patients compared to a control group of 500 patients randomly selected from the hospital. The prevalence of appendectomy in the 2 groups was studied. Results The rate of appendectomy in patients and controls was 26/266 (9.8%) and 27/500 (5.4%), respectively (relative risk 1.30, odds ratio 1.81, χ2, p = 0.026). Appendectomy in the patients was independent of gender (χ2, p = 0.297). Also, there was no difference in patients with and without appendectomy regarding their age, age at diagnosis of PD, and duration of use of levodopa (p = 0.827, 0.960, and 0.688, respectively, Student t test). The mean duration from appendectomy to the diagnosis of the disease varied widely 23 ± 18.7 years, range −12–59 years. Conclusions Appendectomy occurred significantly more frequent in patients with Parkinson’s disease than in control. There was no difference regarding the age of onset of disease in the patients with and without appendectomy. Though the appendix in this study seems to have a protective role against the development of the disease, the relationship is quite complex requiring prospective in-depth evaluation.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

The role of appendectomy in the development of Parkinson’s disease: a retrospective study in a teaching hospital in Jordan

Dahbour

Subuh

Haddad

et al. 2021

Egypt J Neurol Psychiatry Neurosurg

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show abstract

“…Misfolded α-syn aggregates, otherwise known as Lewy body deposits, contribute to the degeneration of dopaminergic neurons within the substantia nigra and other related circuitry (Spillantini et al, 1997(Spillantini et al, , 1998Trojanowski and Lee, 1998), and ultimately the onset of several cardinal motor and non-motor features of PD including dementia, gastrointestinal (GI) dysfunction, tremor, postural instability, bradykinesia, and rigidity (Váradi, 2020). Although most commonly located in the brain, α-syn aggregates have also been found in peripheral locations, such as the enteric nervous system (ENS), lending support to the idea of a "gutbrain axis, " a bidirectional communication pathway between the central and enteric nervous systems and the GI system (Chao et al, 2020; Figure 1).…”

Section: Introductionmentioning

confidence: 95%

The Gut–Brain Axis and Its Relation to Parkinson’s Disease: A Review

Klann

Dissanayake

Gurrala

et al. 2022

Front. Aging Neurosci.

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Parkinson’s disease is a chronic neurodegenerative disease characterized by the accumulation of misfolded alpha-synuclein protein (Lewy bodies) in dopaminergic neurons of the substantia nigra and other related circuitry, which contribute to the development of both motor (bradykinesia, tremors, stiffness, abnormal gait) and non-motor symptoms (gastrointestinal issues, urinogenital complications, olfaction dysfunction, cognitive impairment). Despite tremendous progress in the field, the exact pathways and mechanisms responsible for the initiation and progression of this disease remain unclear. However, recent research suggests a potential relationship between the commensal gut bacteria and the brain capable of influencing neurodevelopment, brain function and health. This bidirectional communication is often referred to as the microbiome–gut–brain axis. Accumulating evidence suggests that the onset of non-motor symptoms, such as gastrointestinal manifestations, often precede the onset of motor symptoms and disease diagnosis, lending support to the potential role that the microbiome–gut–brain axis might play in the underlying pathological mechanisms of Parkinson’s disease. This review will provide an overview of and critically discuss the current knowledge of the relationship between the gut microbiota and Parkinson’s disease. We will discuss the role of α-synuclein in non-motor disease pathology, proposed pathways constituting the connection between the gut microbiome and the brain, existing evidence related to pre- and probiotic interventions. Finally, we will highlight the potential opportunity for the development of novel preventative measures and therapeutic options that could target the microbiome–gut–brain axis in the context of Parkinson’s disease.

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“…These mutations may trigger misfolding and abnormal aggregation . Additionally, α-synuclein amyloid aggregates were discovered in sites other than the brain like the enteric nervous system . Clinicopathological evidence has shown that abnormal aggregation of α-synuclein has been observed in gastrointestinal neurons and gastrointestinal tissue of PD sufferers. , Animal experiments have shown that mice’s duodenum wall is injected with preformed α-synuclein fibrils, resulting in gastrointestinal defects and pathological changes in the intestinal nervous system.…”

Section: Misfolded Proteins Are Like the Black Sheep Are They Infecti...mentioning

confidence: 99%

Amyloid Protein Cross-Seeding Provides a New Perspective on Multiple Diseases In Vivo

Deng

Shi

et al. 2022

Biomacromolecules

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Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.

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

Cited by 22 publications

References 68 publications

The role of appendectomy in the development of Parkinson’s disease: a retrospective study in a teaching hospital in Jordan

The role of appendectomy in the development of Parkinson’s disease: a retrospective study in a teaching hospital in Jordan

The Gut–Brain Axis and Its Relation to Parkinson’s Disease: A Review

Amyloid Protein Cross-Seeding Provides a New Perspective on Multiple Diseases In Vivo

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