Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of PD

Iron Dysregulation and Inflammagens Related to Oral and Gut

Health Are Central to the Development of Parkinson’s Disease

Marthinus Janse van Vuuren 1

, Theodore Albertus Nell 1

, Jonathan Ambrose Carr 2,*, Douglas B. Kell 1,3,4,*

and Etheresia Pretorius 1,*

Citation: Vuuren, M.J.v.; Nell, T.A.;

Carr, J.A.; Kell, D.B.; Pretorius, E.

Iron Dysregulation and

Inflammagens Related to Oral and

Gut Health Are Central to the

Development of Parkinson’s Disease.

Biomolecules 2021, 11, 30. https://

doi.org/10.3390/biom11010030

Received: 12 November 2020

Accepted: 24 December 2020

Published: 29 December 2020

Publisher’s Note: MDPI stays neu-

tral with regard to jurisdictional clai-

ms in published maps and institutio-

nal affiliations.

Copyright: © 2020 by the authors. Li-

censee MDPI, Basel, Switzerland.

This article is an open access article

distributed under the terms and con-

ditions of the Creative Commons At-

tribution (CC BY) license (https://

creativecommons.org/licenses/by/

4.0/).

1 Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Private Bag X1 Matieland,

Stellenbosch 7602, South Africa; mjvanvuuren@sun.ac.za (M.J.v.V.); tnell@sun.ac.za (T.A.N.)

2 Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences,

Stellenbosch University, Private Bag X1 Matieland, Stellenbosch 7602, South Africa

3 Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology,

Faculty of Health and Life Sciences, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK

4 The Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Building 220,

Chemitorvet 200, 2800 Kongens Lyngby, Denmark

* Correspondence: jcarr@sun.ac.za (J.A.C.); dbk@liv.ac.uk (D.B.K.); resiap@sun.ac.za (E.P.)

Abstract: Neuronal lesions in Parkinson’s disease (PD) are commonly associated with α-synuclein

(α-Syn)-induced cell damage that are present both in the central and peripheral nervous systems

of patients, with the enteric nervous system also being especially vulnerable. Here, we bring

together evidence that the development and presence of PD depends on specific sets of interlinking

factors that include neuroinflammation, systemic inflammation, α-Syn-induced cell damage, vascular

dysfunction, iron dysregulation, and gut and periodontal dysbiosis. We argue that there is significant

evidence that bacterial inflammagens fuel this systemic inflammation, and might be central to the

development of PD. We also discuss the processes whereby bacterial inflammagens may be involved

in causing nucleation of proteins, including of α-Syn. Lastly, we review evidence that iron chelation,

pre-and probiotics, as well as antibiotics and faecal transplant treatment might be valuable treatments

in PD. A most important consideration, however, is that these therapeutic options need to be validated

and tested in randomized controlled clinical trials. However, targeting underlying mechanisms of

PD, including gut dysbiosis and iron toxicity, have potentially opened up possibilities of a wide

variety of novel treatments, which may relieve the characteristic motor and nonmotor deficits of PD,

and may even slow the progression and/or accompanying gut-related conditions of the disease.

Keywords: Parkinson’s disease; bacteria; lipopolysaccharides; iron; gingipains; amyloid and α-

synuclein

1. Introduction

The global prevalence of Parkinson’s disease (PD) during 2016 reached 6.1 million [1].

In the United States of America, Canada, and Europe the prevalence is projected to increase

by approximately 92% by 2050 [2], involving an increased burden on global healthcare [3].

α-Synuclein (α-Syn) is the principal component of Lewy bodies (LBs), which are

the pathological hallmark of PD and other related conditions [4]. This group of illnesses,

termed synucleinopathies, includes multisystem atrophy, dementia with Lewy bodies,

and pure autonomic failure. α-Syn-stained inclusion bodies and fragments of neurons are

detectable in many otherwise healthy individuals at the time of postmortem examination

and detailed histological examination has led to conclusion that the initial lesions of PD are

thought to occur in the medulla, in the region of the dorsal motor nucleus of the vagal nerve,

and also in the olfactory bulb [5–7]. In PD patients, LBs are also observed in nondopamin-

ergic neurons outside of the basal ganglia, in areas such as the glossopharyngeal–vagal

complex, coeruleus–subcoeruleus complex, caudal raphe nuclei, gigantocellular reticular

Biomolecules 2021, 11, 30.

Click link below for full review:

 https://doi.org/10.3390/biom11010030

 https://www.mdpi.com/journal/biomolecules