Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease

Vuuren, Marthinus Janse van; Nell, Theo; Carr, Jonathan; Kell, Douglas B.; Pretorius, Etheresia

doi:10.3390/biom11010030

Cited by 19 publications

(31 citation statements)

References 254 publications

(364 reference statements)

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“…In this review, we discussed the link between the BBB disruption and the occurrence of SAE, aiming at finding novel strategies to treat SAE by maintaining the barrier function of BBB. Systemic injection of LPS has been shown to cause damage to the BBB of recipient animals, resulting in the subsequent entry of peripheral cytokines into the brain ( Vuuren et al, 2020 ). It is believed that the main contribution of the damaged BBB to the occurrence and development of SAE is to cause a large number of inflammatory factors and neurotoxins to enter the brain tissue, accompanied by immune cells in the brain tissue such as microglia being activated during systemic inflammation, thereby mediating neuroinflammation and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Blood-Brain Barrier Disruption by Lipopolysaccharide and Sepsis-Associated Encephalopathy

Peng

Luo

et al. 2021

Front. Cell. Infect. Microbiol.

131

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As a complex multicellular structure of the vascular system at the central nervous system (CNS), the blood-brain barrier (BBB) separates the CNS from the system circulation and regulates the influx and efflux of substances to maintain the steady-state environment of the CNS. Lipopolysaccharide (LPS), the cell wall component of Gram-negative bacteria, can damage the barrier function of BBB and further promote the occurrence and development of sepsis-associated encephalopathy (SAE). Here, we conduct a literature review of the direct and indirect damage mechanisms of LPS to BBB and the relationship between these processes and SAE. We believe that after LPS destroys BBB, a large number of inflammatory factors and neurotoxins will enter and damage the brain tissue, which will activate brain immune cells to mediate inflammatory response and in turn further destroys BBB. This vicious circle will ultimately lead to the progression of SAE. Finally, we present a succinct overview of the treatment of SAE by restoring the BBB barrier function and summarize novel opportunities in controlling the progression of SAE by targeting the BBB.

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Section: Discussionmentioning

confidence: 99%

Blood-Brain Barrier Disruption by Lipopolysaccharide and Sepsis-Associated Encephalopathy

Peng

Luo

et al. 2021

Front. Cell. Infect. Microbiol.

131

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“… 6 In addition, the contents of metal elements (e.g., iron, copper, zinc and manganese) in cerebrospinal fluid and brain of patients with PD are much higher than normal ones. Excessive metal concentration involved in the oxidative damage to neuron cells, 3 , 4 particularly iron ions, which react with hydrogen peroxide to generate hydroxyl radicals. 38 The increase of free radicals generates lipid peroxidation, which causes the member damage and cell degeneration.…”

Section: Discussionmentioning

confidence: 99%

“…9 , 10 These abnormal metal elements can cause oxidative damage to dopaminergic neuron cells. 3 , 4 , 7 , 9 Therefore, antioxidant therapy has become one of the treatments of PD. Some drugs have antioxidant neuroprotective effects, can delay the progress of the symptoms of PD in the experimental study, 11 , 12 , 13 , 14 but they still have not proven to be clinically safe or effective.…”

Section: Introductionmentioning

confidence: 99%

In situ analysis of acupuncture protecting dopaminergic neurons from lipid peroxidative damage in mice of Parkinson's disease

et al. 2022

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Objectives Acupuncture stimulation has proven to protect dopaminergic neurons from oxidative damage in animal models of Parkinson's disease (PD), but it remains unclear about the in situ information of biochemical components in dopaminergic neurons. Here, we aimed to analyse in situ changes of biochemical components and lipid peroxidation levels in dopaminergic neurons in PD mice treated with acupuncture by synchrotron FTIR micro‐spectroscopy technique. Materials and Methods About 9–10‐week‐old C57BL/6 mice were used to establish PD model by intraperitoneal injection of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP, 30 mg/kg for 5 days). Acupuncture stimulation was performed once a day for 12 days. Behaviour test was determined using the rotarod instrument. Biochemical compositions of dopaminergic neurons in substantia nigra pars compacta were analysed by synchrotron FTIR micro‐spectroscopy technique. The number and ultrastructure of dopaminergic neurons were respectively observed by immunofluorescence and transmission electron microscopy (TEM). Results We found that the number and protein expression of dopaminergic neurons in MPTP‐treated mice were reduced by about half, while that in the mice treated by acupuncture were significantly restored. Acupuncture treatment also restored the motor ability of PD mice. The results of single cell imaging with synchrotron FTIR micro‐spectroscopy technique showed that the proportion of lipid in MPTP treated mice increased significantly. Especially the ratio of CH 2 asymmetric stretching and CH 3 asymmetric stretching increased significantly, suggesting that MPTP induced lipid peroxidation damage of dopaminergic neurons. It is also supported by the result of TEM, such as mitochondrial swelling or atrophy, loss of mitochondrial crests and mitochondrial vacuolization. Compared with MPTP treated mice, the proportion of lipid in acupuncture treated mice decreased and the mitochondrial structure was restored. Conclusions Acupuncture can inhibit the level of lipid peroxides in dopaminergic neurons and protect neurons from oxidative damage. The study provides a promising method for in situ analysis of biochemical compositions in PD mice and reveals the mechanism of acupuncture in treating neurodegenerative diseases.

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“…However, they can adopt an ominous function and recent studies have shown an association between gut microbiota and neurological disorders (Gorle et al 2021 ). In fact, there are reports suggestive of peripheral inflammation which is prompted by bacterial derived inflammagens which consequently spreads to the brain (Vuuren et al 2020 ). This may play a key role in the development of PD.…”

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confidence: 99%

“…By virtue of eliciting rogue immune reactions, they have the potential in collaboration with other features to unleash deadly pathomechanisms characteristic of the disorder. Indeed, factors such as, α-synuclein aggregates, inflammation in the enteric nervous system and brain, iron elevation in the SN and a disruption of gut flora by some pathogen may contrive to elicit the characteristic neurodegeneration exhibited in the disease (Vuuren et al 2020 ). It therefore may be prudent to explore more carefully the pathways/processes elicited by these pathogens as it may lead to the aetiology of the illness or provide a better understanding of the underlying pathogenesis of PD.…”

mentioning

confidence: 99%

Wilful pathogens provoke a gut feeling in Parkinson’s disease

Sian-Hülsmann

2021

J Neural Transm

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Parkinson’s disease is the second most common neurological disorder marked by characteristic poverty and dysfunction in movement. There are many mechanisms and factors which have been postulated to be associated with the neurodegenerative pathway(s) resulting in distinctive loss of neurons in the substantia nigra. Subsequently, the neuropathology is more widespread and exhibited in other areas of the brain, and enteric nervous system. Aggregates of misfolded α-synuclein or Lewy bodies are the hallmark of the illness and appear to be central in the whole cascade of cell destruction. There are many processes implicated in neuronal destruction including: oxidative stress, excitotoxicity, mitochondrial dysfunction, an imbalance in protein homeostasis and neuroinflammation. Interesting, inflammation induced by pathogens (including, bacteria and viruses) has been associated in the pathogenesis of the disease. Bacteria such as Helicobacter pylori and Helicobacter suis appear to colonise the gut, and elicit systemic immune responses, which is them transmitted via the gut-axis to the brain, where cytotoxic cytokines induce neuroinflammation and cell death. This conforms to the bottom–top hypothesis proposed by Braak. The gut is also implicated in two other theories postulated in the development and progression of the disorder, namely, the top–down and the threshold. There is a possibility that these theories may be inter-linked and operate together to certain degree. Ultimately specific trigger factors or conditions may govern the occurrences of these processes in genetically predisposed individuals. Nevertheless, the importance of pathogen-related gut infections cannot be overlooked, since it can result in dysbiosis of gut microbes, which may orchestrate α-synuclein pathology and eventually cell destruction.

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Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease

Cited by 19 publications

References 254 publications

Blood-Brain Barrier Disruption by Lipopolysaccharide and Sepsis-Associated Encephalopathy

Blood-Brain Barrier Disruption by Lipopolysaccharide and Sepsis-Associated Encephalopathy

In situ analysis of acupuncture protecting dopaminergic neurons from lipid peroxidative damage in mice of Parkinson's disease

Wilful pathogens provoke a gut feeling in Parkinson’s disease

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