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

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.

Bacteria, Lipopolysaccharides, Amyloid and the Role of Iron Dysregulation in Parkinson’s Disease

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 neuro-inflammation, systemic inflammation, α-Syn-induced cell damage, vascular dysfunction, iron dysregulation, 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 lipopolysaccharides may be involved in causing nucleation of proteins, including of α-Syn. Lastly, we review evidence that 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 non-motor deficits of PD, and may even slow the progression and/or accompanying gut-related conditions of the disease.

COVID-19 Immunopathology, Particle Pollution, and Iron Balance

The coronavirus (COVID-19) pandemic exploded into a world already reeling from climate change, degradation of natural systems, and pandemics of air pollution and noncommunicable diseases. These pandemics are interrelated; air pollution, the world’s biggest killer, is a major contributor to noncommunicable disease. Air pollution is a probable cofactor in the spread and severity of COVID-19. There are shared mechanisms of injury by the emerging COVID-19 immunopathology, ultrafine air pollutants, and chronic degenerative disease. A key feature of each is oxidative stress, including that caused by iron dysregulation. Exogenous combustion-derived magnetite nanoparticles found in human brains and hearts are strongly implicated in the development of cardiometabolic and neurogenerative disease. Altered iron balance favoring excess reactive or misplaced iron is probably the most important predisposing condition for severe COVID-19 infection. Ultrafine-particle/nanoparticle toxicity and COVID-19 immunopathology on the subcellular level are both characterized by iron dysregulation, mitochondrial dysfunction, and endoplasmic reticulum stress. Primary sources of the most damaging ultrafine pollution particles are fossil fuel combustion, vehicle emissions, and coal fly ash utilized in undisclosed tropospheric aerosol geoengineering. The same ultrafine particles when emitted or placed into the troposphere alter the world’s cloud layers and reduce atmospheric convection, directly contributing to climate change and global warming. Pandemics can only be tackled by international cooperation. Immediate steps that must be taken include monitoring and control of ultrafine particulate air pollution, and prompt cessation of geoengineering operations.

Serial assessment of iron in the motor cortex in limb-onset Amyotrophic Lateral Sclerosis using Quantitative Susceptibility Mapping

ABSTRACTObjectiveDysregulation of iron in the cerebral motor areas has been hypothesized to occur in individuals with Amyotrophic Lateral Sclerosis (ALS). There is still limited knowledge regarding iron dysregulation in the progression of ALS pathology. Our objectives were to use magnetic resonance based Quantitative Susceptibility Mapping (QSM) to investigate the association between iron dysregulation in the motor cortex and clinical manifestations in patients with limb-onset ALS, and to examine changes in the iron concentration in the motor cortex in these patients over a six-month period.MethodsIron concentration was investigated using magnetic resonance based -QSM in the primary motor cortex and the pre-motor area in thirteen limb-onset ALS patients (including five lumbar onset, six cervical onset and two flail arm patients), and eleven age and sex-matched healthy controls. Nine ALS patients underwent follow-up scans at six months.ResultsSignificantly increased QSM was observed in the left posterior primary motor area (p = 0.02, Cohen’s d = 0.9) and right anterior primary motor area (p = 0.02, Cohen’s d = 0.92) in all individuals with limb-onset ALS compared to healthy controls. Increased QSM was observed in the primary motor and pre-motor area at baseline in patients with lumbar onset ALS patients, but not cervical limb-onset ALS patients, compared to healthy controls. No significant change in QSM was observed at the six-month follow-up scans in the ALS patients.ConclusionsThe findings suggest that iron dysregulation can be detected in the motor cortex in limb-onset ALS, which does not appreciably change over a further 6 months. Individuals with lumbar onset ALS appear to be more susceptible to motor cortex iron dysregulation compared to the individuals with cervical onset ALS. Importantly, this study highlights the potential use of QSM as a radiological indicator in disease diagnosis, and in clinical trials in limb-onset ALS and its subtypes.HighlightsSerial measurement of QSM in the motor cortex in limb-onset ALS was performedQSM changes in the motor cortex in ALS sub-groups were investigatedHigher QSM was observed in the motor cortex in Lumbar ALS relative to controlsQSM is sensitive to iron dysregulation in the motor cortex in limb-onset ALS