Iron dysregulation and inflammagens related to oral and gut health are central to the development of parkinson’s disease

Marthinus Janse van Vuuren, Theodore Albertus Nell, Jonathan Ambrose Carr*, Douglas B. Kell, Etheresia Pretorius

*Corresponding author for this work

Research output: Contribution to journalReviewResearchpeer-review

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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.

Original languageEnglish
Article number30
JournalBiomolecules
Volume11
Issue number1
Pages (from-to)1-27
ISSN2218-273X
DOIs
Publication statusPublished - Jan 2021

Bibliographical note

Funding Information:
This research was funded by the Medical Research Council of South Africa (MRC), grant number: A0 ? 331 Self-initiated research, and The Novo Nordisk Foundation, grant number: NNF10CC1016517.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Amyloid and α-synuclein
  • Bacteria
  • Gingipains
  • Iron
  • Lipopolysaccharides
  • Parkinson’s disease

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