scholarly journals Iron dysregulation in COVID‐19 and reciprocal evolution of SARS‐CoV‐2: Natura nihil frustra facit

2022 ◽  
Author(s):  
Yash Gupta ◽  
Dawid Maciorowski ◽  
Brian Medernach ◽  
Daniel P. Becker ◽  
Ravi Durvasula ◽  
...  
Keyword(s):  
Iron Dysregulation

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

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 30
Author(s):  
Marthinus Janse van Vuuren ◽  
Theodore Albertus Nell ◽  
Jonathan Ambrose Carr ◽  
Douglas B. Kell ◽  
Etheresia Pretorius
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Systemic Inflammation ◽  
Cell Damage ◽  
Vascular Dysfunction ◽  
Iron Chelation ◽  
Gut Health ◽  
Novel Treatments ◽  
Randomized Controlled Clinical Trials ◽  
Iron Dysregulation

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.

scholarly journals Lipocalin 2 contributes to brain iron dysregulation but does not affect cognition, plaque load, and glial activation in the J20 Alzheimer mouse model

2018 ◽  
Vol 15 (1) ◽  
Author(s):  
Doortje W. Dekens ◽  
Petrus J. W. Naudé ◽  
Jan N. Keijser ◽  
Ate S. Boerema ◽  
Peter P. De Deyn ◽  
...  
Keyword(s):  
Mouse Model ◽  
Glial Activation ◽  
Lipocalin 2 ◽  
Brain Iron ◽  
Plaque Load ◽  
Iron Dysregulation

scholarly journals Iron dysregulation: an important aspect in toxicology

2010 ◽  
Vol 84 (11) ◽  
pp. 823-824 ◽  
Author(s):  
H. M. Bolt ◽  
R. Marchan
Keyword(s):  
Iron Dysregulation

scholarly journals Hyperphosphatemia Contributes to Inflammation and Iron Dysregulation in Models of Normal and Impaired Renal Function

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2238-2238
Author(s):  
Brian Czaya ◽  
Beatrice Richter ◽  
Christopher Yanucil ◽  
Isaac Campos ◽  
Kylie Heitman ◽  
...  
Keyword(s):  
Renal Function ◽  
Inflammatory Cytokines ◽  
Systemic Inflammation ◽  
Iron Metabolism ◽  
Impaired Renal Function ◽  
Conflicts Of Interest ◽  
Experimental Studies ◽  
Dependent Manner ◽  
Primary Mouse ◽  
Iron Dysregulation

Background Fibroblast growth factor (FGF) 23 is a phosphaturic hormone that targets the kidney to promote urinary phosphate excretion. In patients with chronic kidney disease (CKD), serum concentrations of phosphate (Pi) and FGF23 gradually increase as renal function declines and associate with various pathologies, including systemic inflammation and anemia. Our previous studies revealed FGF23 contributes to inflammation by directly targeting hepatocytes via FGF receptor 4 (FGFR4) and inducing phospholipase Cγ (PLCγ) signaling and the expression of inflammatory cytokines. Experimental studies have shown Pi can accelerate CKD-associated pathologies, but direct effects of Pi on the liver are not well described. Here we compare the effects of Pi versus FGF23 on hepatocytes and determine their respective contributions to inflammation and anemia in the context of CKD. Methods We subject mice with global deletion of FGFR4 and wild-type littermates to increasing dietary Pi load (0.7%, 2.0%, or 3.0%) or an adenine-rich diet (used as a CKD model) in order to examine systemic inflammation and alterations in iron metabolism in the setting of normal and impaired renal function. In addition, we study primary mouse hepatocytes treated with FGF23 and increasing Pi concentrations and examine the activation of downstream signaling events and expression levels of specific target genes. Furthermore, we determine if co-treatment with inhibitors of Pi uptake and downstream signal mediators block the observed effects. Results A 3% Pi diet as well as an adenine-rich diet promote inflammation and iron dysregulation in mice. These effects are exacerbated in FGFR4 knockout mice. In cultured hepatocytes, expression of inflammatory cytokines, hepcidin and FGF23 are induced by Pi in a dose-dependent manner. Furthermore, Pi activates NFkB signaling and the inhibition of Pi uptake and of NFkB protects from Pi-induced effects. Conclusion We postulate that in CKD, gradual elevations in serum Pi promote inflammation and anemia by targeting the liver to induce gene programs which regulate the inflammatory response and iron metabolism. Our study indicates these Pi effects may be independent of FGF23. Pharmacological approaches targeting hyperphosphatemia or hepatic Pi actions might alleviate various CKD-associated pathologies. Disclosures No relevant conflicts of interest to declare.

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

2020 ◽  
Author(s):  
Marthinus Janse van Vuuren ◽  
Theodore Albertus Nell ◽  
Jonathan Ambrose Carr ◽  
Douglas B Kell ◽  
Etheresia Pretorius
Keyword(s):  
Systemic Inflammation ◽  
Cell Damage ◽  
Vascular Dysfunction ◽  
Alpha Synuclein ◽  
Motor Deficits ◽  
Novel Treatments ◽  
Randomized Controlled Clinical Trials ◽  
Iron Dysregulation ◽  
Neuro Inflammation ◽  
Underlying Mechanisms

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.

Iron Dysregulation in Parkinson’s Disease: Focused on the Autophagy–Lysosome Pathway

2018 ◽  
Vol 10 (2) ◽  
pp. 863-871 ◽  
Author(s):  
Lei-Lei Chen ◽  
Yu-Jv Huang ◽  
Jun-tao Cui ◽  
Ning Song ◽  
Junxia Xie
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Iron Dysregulation
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