Parkinson's Disease {40000200}
Definition: | Parkinson's Disease |
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Class: | [ ] |
Other Terms: | PD |
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Authoring date: | 2021-02-05 |
ICD: | [ ] |
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Category: | Neurologic |
MedDra ID: | 10061536 |
MedDra Level: | pt |
Notes
Shared Notes
- [1.28]
- Gut-to-brain propagation of pathologic α-synuclein via the vagus nerve causes PD
- Dopamine neurons degenerate in the pathologic α-synuclein gut-to-brain model of PD
- Gut injection of pathologic α-synuclein causes PD-like motor and non-motor symptoms
- PD-like pathology and symptoms require endogenous α-synuclein. - [1.29]
- The most common bacteria found in the stool samples are: Bacteroides, Faecalibacerium, Gemmiger, Roseburia, Prevotella, and Ruminococcus.
- Severe constipation > Decreased Faecalibacterium.
- Lowest physical activity and severe constipation > Increased Firmicutes
- High physical activity > Increased Bacteroides. - [1.30]
- The gastrointestinal tract is the major site for L-dopa decarboxylation
- L-dopa > decarboxylation > generation of dopamine in the periphery > cannot cross the blood-brain barrier and causes unwanted side effects.
- L-dopa is coadministered with drugs that block peripheral metabolism, including the AADC inhibitor carbidopa.
- Even with carbidopa, up to 56% of L-dopa fails to reach the brain.
- Enterococcus faecalis (enzyme (PLP-dependent tyrosine decarboxylase or TyrDC)) consume dopamine > producing meta-tyramine as a by-product > may contribute to some of the noxious L-dopa side effects.
- carbidopa may not be able to penetrate the microbial cells or the slight structural variance could prevent the drug from interacting with the bacterial enzyme. - [1.31]
- The relative abundance of mucin-degrading Verrucomicrobiae and LPS-producing Gammaproteobacteria were greater in PD patients.
- Severe patients exhibited elevated levels of Verrucomicrobiae.
- High levels of Verrucomicrobiae in the severe PD may increase intestinal leakiness, facilitating translocation of luminal LPS to the enteric nervous system or systemic circulation.
- Systemic LPS has been linked to intestinal inflammation, which in turn is associated with enteric Thy1-αSyn aggregation. - [1.32]
- Patients with inflammatory bowel disease are more likely to develop Parkinson disease.
- People receiving drugs used to reduce inflammation—tumor necrosis factor (TNF) inhibitors—the incidence of the neurodegenerative disease dropped significantly.
- Chronically inflamed gut may elevate alpha-synuclein levels locally and give rise to inflammation throughout the body, which in itself could increase the permeability of the gut and blood-brain barriers.
- Circulating cytokines are increased that can promote inflammation. - [1.33]
- Overabundance of opportunistic pathogens in PD gut is influenced by the host genotype at the alpha-synuclein locus. - [1.34]
- There is a lower fungal DNA relative to bacterial DNA among PD patients.
- No fungi differed in abundance.
- No fungi association with motor, cognitive, or gastrointestinal features among PD patients. - [1.35]
- Later age of onset correlated most strongly with MIND diet (Mediterranean diet and the DASH "Dietary Approaches to Stop Hypertension" diet) adherence in the females PD Patient
- Greek Mediterranean adherence is associated with later PD onset - [1.21]
- FABP6 (fatty acid binding protein 6) is the intracellular bile acid transporter which returns bile acids to enterohepatic circulation.
- In Parkinson Disease, ileum and appendix had a strong decrease in fatty acid binding protein 6 (FABP6) and a decrease in lipid metabolism.
- Primary bile acids or total bile acid levels in the PD appendix are not changed.
- Secondary bile acids produced by the microbiota are elevated PD appendix. - [1.36]
Toxic Bile acids produced by specifics Clostridium species may predispose to PD - [1.37]
- PD is not one, but two diseases.
- Some patients had damage to the brains dopamine system before damage in the intestines and heart occurred.
- In other patients, scans revealed damage to the nervous systems of the intestines and heart before the damage in the brains dopamine system was visible - [1.38]
- PINK1 is a repressor of the immune system, and provide a pathophysiological model in which intestinal infection acts as a triggering event in Parkinson’s disease
- The infection of mice that did not express PINK1 and/or PRKN with the Gram-negative bacterium Citrobacter rodentium triggered mitochondrial antigen presentation in the periphery. Furthermore, the intestinal infection led to cytotoxic CD8+ T cells being established, which targeted dopaminergic neurons in the brain, whereas non-dopaminergic neurons were not affected - [1.27]
- The relative abundance of Enterobacteriaceae is positively associated with the severity of postural instability and gait difficulty. - [1.25]
- Increase of D-Laktat und Glykolat has amelorative effects on Parkinson disease.
- D-Laktat is produced by lactobacillus bulgaricus. - [1.39]
- In 1817, the English surgeon James Parkinson described some of the first cases of the “shaking palsy” that would come to be known as Parkinson’s disease.
- One individual had developed numbness and prickling sensations in both arms. Parkinson noticed that the man’s abdomen seemed to contain “considerable accumulation”. He dosed the man with a laxative, and ten days later his bowels were empty and his symptoms were gone.
Common References
- [1.1] The oral microbiome of early stage Parkinson's disease and its relationship with functional measures of motor and non-motor function. [2019] [80001206] [PLOS ONE]
- [1.2] Alteration of the fecal microbiota in Chinese patients with Parkinson's disease [2018] [80000645] [Brain, Behavior, and Immunity]
- [1.3] The nasal and gut microbiome in Parkinson's Disease and Idiopathic Rapid Eye Movement Sleep Behavior Disorder [2018] [80000656] [Movement Disorders]
- [1.4] Colonic bacterial composition in Parkinson's Disease [2015] [80000275] [Movement Disorders]
- [1.5] Parkinson's Disease and Parkinson's Disease medications have distinct signatures of the gut microbiome. [2017] [80000277] [Movement Disorders]
- [1.6] Unraveling gut microbiota in Parkinson's Disease and Atypical Parkinsonism [2019] [80000955] [Movement Disorders]
- [1.7] Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson's disease [2019] [80001105] [Journal of Neuroinflammation]
- [1.8] A pilot microbiota study in Parkinson's Disease patients versus control subjects, and effects of FTY720 and FTY720-Mitoxy therapies in Parkinsonian and multiple system atrophy mouse models [2020] [80001285] [Journal of Parkinson's Disease]
- [1.9] Alteration of the fecal microbiota in North-Eastern Han Chinese population with sporadic Parkinson's disease [2019] [80001306] [Neuroscience Letters]
- [1.10] Meta-analysis of gut dysbiosis in Parkinson's Disease [2020] [80001422] [Movement Disorders]
- [1.11] Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls [2016] [80000274] [Parkinsonism and Related Disorders]
- [1.12] Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naïve Parkinson's disease patients. [2017] [80000464] [Genome Medicine]
- [1.13] Gut microbiota altered in mild cognitive impairment compared with normal cognition in sporadic Parkinson's disease [2020] [80001370] [Frontiers in Neurology]
- [1.14] Gut microbiota in patients with Parkinson's disease in southern China [2018] [80000788] [Parkinsonism and Related Disorders]
- [1.15] Gut microbiota differs between parkinson's disease patients and healthy controls in northeast China [2019] [80001147] [Frontiers in Molecular Neuroscience]
- [1.16] Gut microbiota in Parkinson's disease: temporal stability and relations to disease progression [2019] [80001183] [EBioMedicine]
- [1.17] Gut microbiota in Parkinson Disease in a northern German cohort [2017] [80000463] [Brain Research]
- [1.18] Analysis of gut microbiota in patients with Parkinson's Disease [2017] [80000604] [Bulletin of Experimental Biology and Medicine]
- [1.19] Dysbiosis of gut microbiota in a selected population of Parkinson's patients [2019] [80001078] [Parkinsonism and Related Disorders]
- [1.20] Detection of microbial 16S rRNA gene in the blood of patients with Parkinson's Disease [2018] [80001148] [Frontiers in Aging Neuroscience]
- [1.21] Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease [2021] [Research] [80001617] [Metabolites]
- [1.22] Oral and nasal microbiota in Parkinson's disease [2017] [80000279] [Parkinsonism and Related Disorders]
- [1.23] Structural changes of gut microbiota in Parkinson's disease and its correlation with clinical features. [2017] [80000601] [Science China Life Sciences]
- [1.24] Intestinal Dysbiosis and lowered Serum lipopolysaccharide-binding protein in Parkinson's Disease [2015] [80000278] [PLOS ONE]
- [1.25] Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival [2014] [Review] [80001631] [Biology Open]
- [1.26] Oral and nasal microbiota in Parkinsonis's disease [2017] [80000605] [Parkinsonism and Related Disorders]
- [1.27] Gut microbiota are related to Parkinson's Disease and clinical phenotype [2015] [Research] [80000276] [Movement Disorders]
- [1.28] Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease [2019] [Research] [80000064] [Neuron]
- [1.29] Gut microbiome signatures of risk and prodromal markers of Parkinson’s disease [2019] [Research] [80000177] [bioRxiv]
- [1.30] Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism_2 [2019] [Research] [80000048] [Science]
- [1.31] Altered Gut Microbiome in Parkinson’s Disease and the Influence of Lipopolysaccharide in a Human α-Synuclein Over-Expressing Mouse Model [2019] [Review] [80000100] [Frontiers in Neuroscience]
- [1.32] Anti–Tumor Necrosis Factor Therapy and Incidence of Parkinson Disease Among Patients With Inflammatory Bowel Disease [2018] [Research] [80001576] [JAMA Neurology]
- [1.33] Human-genome gut-microbiome interaction in Parkinson's disease [2021] [Abstract] [80001580] [bioRxiv]
- [1.34] The Gut Mycobiome in Parkinson’s Disease [2021] [Abstract] [80001585] [Journal of Parkinson's Disease]
- [1.35] MIND and Mediterranean Diets Associated with Later Onset of Parkinson's Disease [2021] [Research] [80001507] [Movement Disorders]
- [1.36] The vermiform appendix impacts the risk of developing Parkinson’s disease [2021] [Research] [80001628] [Metabolites]
- [1.37] Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study [2020] [Research] [80001629] [Brain]
- [1.38] Intestinal infection triggers Parkinson’s disease-like symptoms in Pink1−/− mice [2019] [Abstract] [80001630] [Nature]
- [1.39] How gut microbes could drive brain disorders [2021] [Review] [80001620] [Nature]