The Intestinal Barrier in Parkinson's Disease: Current State of Knowledge

Overview

Journal J Parkinsons Dis

Publisher Sage Publications

Specialty Neurology

Date 2019 Sep 29

PMID 31561386

Citations 40

Authors

Sven C D van Ijzendoorn

Pascal Derkinderen

Affiliations

Soon will be listed here.

Abstract

The intestinal barrier, which primarily consists of epithelial cells stitched together with connecting proteins called tight junctions, plays a critical role in health and disease. It is in close contact with the gut microbiota on its luminal side and with the enteric neurons on the tissue side. Both microbiota and the enteric nervous system are regulatory housekeepers of the intestinal barrier. Therefore, the recently observed enteric neuropathology along with gut dysbiosis in Parkinson's disease have prompted research on intestinal permeability in this neurodegenerative disorder. In this mini-review we attempt to concisely summarize the current knowledge on intestinal barrier in Parkinson's disease. We envision future direction research that should be pursued in order to demonstrate its possible role in disease development and progression.

Citing Articles

Correlations Between Amelioration of Rotenone-Induced Parkinson's Symptoms by Flavonoids and Gut Microbiota in Mice.

Liu L, Zhao Y, Yang W, Han L, Mo X, Sheng J Int J Mol Sci. 2025; 26(4).

PMID: 40004140 PMC: 11855768. DOI: 10.3390/ijms26041676.

The epithelial barrier theory and its associated diseases.

Sun N, Ogulur I, Mitamura Y, Yazici D, Pat Y, Bu X Allergy. 2024; 79(12):3192-3237.

PMID: 39370939 PMC: 11657050. DOI: 10.1111/all.16318.

Gut-brain axis: A cutting-edge approach to target neurological disorders and potential synbiotic application.

Ashique S, Mohanto S, Ahmed M, Mishra N, Garg A, Chellappan D Heliyon. 2024; 10(13):e34092.

PMID: 39071627 PMC: 11279763. DOI: 10.1016/j.heliyon.2024.e34092.

Lifestyle Changes and Industrialization in the Development of Allergic Diseases.

Ozdemir C, Kucuksezer U, Ogulur I, Pat Y, Yazici D, Ardicli S Curr Allergy Asthma Rep. 2024; 24(7):331-345.

PMID: 38884832 PMC: 11233349. DOI: 10.1007/s11882-024-01149-7.

Systematic-Narrative Hybrid Literature Review: Crosstalk between Gastrointestinal Renin-Angiotensin and Dopaminergic Systems in the Regulation of Intestinal Permeability by Tight Junctions.

Khan N, Kurnik-Lucka M, Latacz G, Gil K Int J Mol Sci. 2024; 25(10).

PMID: 38791603 PMC: 11122119. DOI: 10.3390/ijms25105566.

References

Prigent A, Gonzales J, Durand T, Le Berre-Scoul C, Rolli-Derkinderen M, Neunlist M . Acute inflammation down-regulates alpha-synuclein expression in enteric neurons. J Neurochem. 2018; 148(6):746-760. DOI: 10.1111/jnc.14656. View

Workman M, Mahe M, Trisno S, Poling H, Watson C, Sundaram N . Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nat Med. 2016; 23(1):49-59. PMC: 5562951. DOI: 10.1038/nm.4233. View

Kuan W, Bennett N, He X, Skepper J, Martynyuk N, Wijeyekoon R . α-Synuclein pre-formed fibrils impair tight junction protein expression without affecting cerebral endothelial cell function. Exp Neurol. 2016; 285(Pt A):72-81. DOI: 10.1016/j.expneurol.2016.09.003. View

van Elburg R, Uil J, Kokke F, Mulder A, van de Broek W, Mulder C . Repeatability of the sugar-absorption test, using lactulose and mannitol, for measuring intestinal permeability for sugars. J Pediatr Gastroenterol Nutr. 1995; 20(2):184-8. DOI: 10.1097/00005176-199502000-00008. View

Juuti-Uusitalo K, Klunder L, Sjollema K, Mackovicova K, Ohgaki R, Hoekstra D . Differential effects of TNF (TNFSF2) and IFN-γ on intestinal epithelial cell morphogenesis and barrier function in three-dimensional culture. PLoS One. 2011; 6(8):e22967. PMC: 3154921. DOI: 10.1371/journal.pone.0022967. View

Bischoff S, Barbara G, Buurman W, Ockhuizen T, Schulzke J, Serino M . Intestinal permeability--a new target for disease prevention and therapy. BMC Gastroenterol. 2014; 14:189. PMC: 4253991. DOI: 10.1186/s12876-014-0189-7. View

Hill D, Huang S, Nagy M, Yadagiri V, Fields C, Mukherjee D . Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium. Elife. 2017; 6. PMC: 5711377. DOI: 10.7554/eLife.29132. View

Braak H, de Vos R, Bohl J, Del Tredici K . Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett. 2005; 396(1):67-72. DOI: 10.1016/j.neulet.2005.11.012. View

Holmqvist S, Chutna O, Bousset L, Aldrin-Kirk P, Li W, Bjorklund T . Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol. 2014; 128(6):805-20. DOI: 10.1007/s00401-014-1343-6. View

10.

Schwiertz A, Spiegel J, Dillmann U, Grundmann D, Burmann J, Fassbender K . Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson's disease. Parkinsonism Relat Disord. 2018; 50:104-107. DOI: 10.1016/j.parkreldis.2018.02.022. View

11.

Kim S, Kwon S, Kam T, Panicker N, Karuppagounder S, Lee S . Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease. Neuron. 2019; 103(4):627-641.e7. PMC: 6706297. DOI: 10.1016/j.neuron.2019.05.035. View

12.

Choi J, Kim N, Ju I, Eo H, Lim S, Jang S . Oral administration of Proteus mirabilis damages dopaminergic neurons and motor functions in mice. Sci Rep. 2018; 8(1):1275. PMC: 5775305. DOI: 10.1038/s41598-018-19646-x. View

13.

Hernandez-Romero M, Delgado-Cortes M, Sarmiento M, de Pablos R, Espinosa-Oliva A, Arguelles S . Peripheral inflammation increases the deleterious effect of CNS inflammation on the nigrostriatal dopaminergic system. Neurotoxicology. 2012; 33(3):347-60. DOI: 10.1016/j.neuro.2012.01.018. View

14.

Giepmans B, van Ijzendoorn S . Epithelial cell-cell junctions and plasma membrane domains. Biochim Biophys Acta. 2008; 1788(4):820-31. DOI: 10.1016/j.bbamem.2008.07.015. View

15.

Reale M, Iarlori C, Thomas A, Gambi D, Perfetti B, Di Nicola M . Peripheral cytokines profile in Parkinson's disease. Brain Behav Immun. 2008; 23(1):55-63. DOI: 10.1016/j.bbi.2008.07.003. View

16.

Schulzke J, Gitter A, Mankertz J, Spiegel S, Seidler U, Amasheh S . Epithelial transport and barrier function in occludin-deficient mice. Biochim Biophys Acta. 2005; 1669(1):34-42. DOI: 10.1016/j.bbamem.2005.01.008. View

17.

McCracken K, Howell J, Wells J, Spence J . Generating human intestinal tissue from pluripotent stem cells in vitro. Nat Protoc. 2011; 6(12):1920-8. PMC: 3896236. DOI: 10.1038/nprot.2011.410. View

18.

Hill D, Spence J . Gastrointestinal Organoids: Understanding the Molecular Basis of the Host-Microbe Interface. Cell Mol Gastroenterol Hepatol. 2017; 3(2):138-149. PMC: 5331777. DOI: 10.1016/j.jcmgh.2016.11.007. View

19.

Perez-Pardo P, Dodiya H, Engen P, Forsyth C, Huschens A, Shaikh M . Role of TLR4 in the gut-brain axis in Parkinson's disease: a translational study from men to mice. Gut. 2018; 68(5):829-843. DOI: 10.1136/gutjnl-2018-316844. View

20.

Van Den Berge N, Ferreira N, Gram H, Mikkelsen T, Alstrup A, Casadei N . Evidence for bidirectional and trans-synaptic parasympathetic and sympathetic propagation of alpha-synuclein in rats. Acta Neuropathol. 2019; 138(4):535-550. PMC: 6778265. DOI: 10.1007/s00401-019-02040-w. View