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Parkinsons - Just another Infectious Disease | OMICS International
E-ISSN: 2314-7326
P-ISSN: 2314-7334
Journal of Neuroinfectious Diseases
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Parkinsons - Just another Infectious Disease

Coad Thomas Dow*
McPherson Eye Research Institute, Wisconsin, USA
Corresponding Author : Coad Thomas Dow
McPherson Eye Research Institute, Ophthalmology
2715 Damon Street Eau Claire
Wisconsin 54701, USA
Tel: +01-715-834-8471
E-mail: [email protected]
Received: June 26, 2015 Accepted: July 16, 2015 Published: July 24, 2015
Citation: Dow CT (2015) Parkinson’s - Just another Infectious Disease. J Neuroinfect Dis 6:183. doi:/10.4172/2314-7326.1000183
Copyright: © 2015 Dow CT. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract

Anatomic staging of PD progression suggests that an unidentified neurotropic pathogen in the intestinal lumen triggers abnormal synuclein aggregation that, in turn, initiates a ''prion-like'' process in the enteric nervous system (ENS) eventually achieving access to the central nervous system (CNS) via the vagus nerve (cranial nerve X). This protein aggregation, manifest as  , targets and destroys dopamine producing cells resulting in both the classic motor and non-motor symptoms of PD; with the non-motor symptoms predating the motor symptoms by years, or even decades.

Abstract

Anatomic staging of PD progression suggests that an unidentified neurotropic pathogen in the intestinal lumen triggers abnormal synuclein aggregation that, in turn, initiates a ''prion-like'' process in the enteric nervous system (ENS) eventually achieving access to the central nervous system (CNS) via the vagus nerve (cranial nerve X). This protein aggregation, manifest as Lewy bodies, targets and destroys dopamine producing cells resulting in both the classic motor and non-motor symptoms of PD; with the non-motor symptoms predating the motor symptoms by years, or even decades.
Commentary

Neuroscientists are turning - or shall we say returning - to the intestinal tract to study Parkinson’s disease (PD). James Parkinson, in 1817, posed the following:

“Although unable to trace the connection by which a disordered state of the stomach and bowels may induce a morbid action in a part of the medulla spinalis, little hesitation need be employed before we determine on the probability of such occurrence” [1].

Anatomic staging of PD progression suggests that an unidentified neurotropic pathogen in the intestinal lumen triggers abnormal synuclein aggregation that, in turn, initiates a ‘‘prion-like’’ process in the enteric nervous system (ENS) eventually achieving access to the central nervous system (CNS) via the vagus nerve (cranial nerve X) [2-7]. This protein aggregation, manifest as Lewy bodies, targets and destroys dopamine producing cells resulting in both the classic motor and non-motor symptoms of PD [7,8]; with the non-motor symptoms predating the motor symptoms by years, or even decades [9].

Genetic studies reveal an association between (PD), leprosy and Crohn’s disease and since discovered, these findings have been considered ‘‘surprising’’. Autophagy and ubiquitin-proteosome systems are cellular systems that both fight intracellular pathogens (xenophagy) and maintain cellular protein quality control. PD is a common neurodegenerative disease that manifests clinically as a profound movement disorder. The recognized genetic defects of PD create disruption of cellular homeostasis that result in protein folding abnormalities of PD called Lewy bodies. Those same genetic defects are associated with susceptibility to intracellular pathogens, including mycobacteria. It is now understood that PD Lewy body pathology starts in the enteric nervous system and ‘‘spreads’’ to the brain in a retrograde fashion via the vagus nerve [10].

An accurate early diagnostic test for Parkinson’s disease (PD) is a critical unmet need [11]. Analysis of the ENS by routine colonoscopy biopsies is evolving as a tool for pre-mortem neuropathological diagnosis of PD, and also provides insight into the progression of motor and non-motor symptoms [12].

It seems that in PD something is perturbing the microbiome of the gut [13]. I have suggested a triggering role for Mycobacterium avium ss. paratuberculosis (MAP) [10]. It could be MAP and/or a host of other infectious/noxious precipitants of the protein cascade that results in PD, but the gut is a reasonable place to start; because when it comes to PD: what happens in the vagus does not stay in the vagus.
References

  1. Parkinson J (1817) An essay on the shaking palsy. Whittingham and Rowland, London.

  2. Trojanowski JQ, Lee VM (1998) Aggregation of neurofilament and alpha-synuclein proteins in Lewy bodies: implications for the pathogenesis of Parkinson disease and Lewy body dementia. Arch Neurol 55: 151-152.

  3. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, et al. (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24: 197-211.

  4. Gray MT, Munoz DG, Gray DA, Schlossmacher MG, Woulfe JM (2013) Alpha-synuclein in the appendiceal mucosa of neurologically intact subjects. MovDisord 29: 991-998.

  5. Ulusoy A, Rusconi R, PÈrez-Revuelta BI, Musgrove RE, Helwig M, et al. (2013) Caudo-rostral brain spreading of alpha-synuclein through vagal connections. EMBO Mol Med 5: 1051-1059

  6. Ferrer I, Martinez A, Blanco R, Dalfó E, Carmona M (2011) Neuropathology of sporadic Parkinson disease before the appearance of parkinsonism: preclinical Parkinson disease. J Neural Transm 118: 821-839.

  7. Olanow CW (2014) Do prions cause Parkinson disease?: the evidence accumulates. Ann Neurol 75: 331-333.

  8. Costanzo M, Zurzolo C (2013) The cell biology of prion-like spread of protein aggregates: mechanisms and implication in neurodegeneration. Biochem J 452:1-17.

  9. Gelb DJ, Oliver E, Gilman S (1999) Diagnostic criteria for Parkinson disease. Arch Neurol 56: 33-39.

  10. Dow CT (2014) M. paratuberculosis and Parkinson's disease--is this a trigger. Med Hypotheses. 83: 709-712.

  11. Visanji NP, Marras C, Hazrati LN, Liu LW, Lang AE (2014) Alimentary, my dear Watson? The challenges of enteric α-synuclein as a Parkinson's disease biomarker.   MovDisord 29: 444-450.

  12. Lebouvier T, Neunlist M, Bruley des Varannes S, Coron E, Drouard A, et al. (2010) Colonic biopsies to assess the neuropathology of Parkinson's disease and its relationship with symptoms.  PLoS One 5: e12728.

  13. Friedland RP (2015) Mechanisms of molecular mimicry involving the microbiota in neurodegeneration.  J Alzheimers Dis 45: 349-362.

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