Iron as Therapeutic Target in Human Diseases

Gozzelino, Raffaella; Poli, Maura; Arosio, Paolo

doi:10.3390/ph12040178

Cited by 4 publications

(3 citation statements)

References 50 publications

(48 reference statements)

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“…Our data found no increase in the accumulation of Fe in mice exposed or not to MPTP when comparing young vs. old animals (Figure 3). This data confirmed that increased Fe levels occur throughout the lifetime [31,32,63] and are not detected prior to disease onset [31,32,[40][41][42]. Sequestered in peripheral immune cells, Fe circulates and enters the brain.…”

Section: Discussionsupporting

confidence: 71%

“…Hence, the disruption of Fe homeostasis in the brain strongly contributes to neuroinflammation and sensitizes disease onset, as previously reported [60]. Fe is highly abundant in the brain, where it is involved in many biological functions [32,33,41,42]. Its ability to undergo oxidation and reduction reactions, exchanging electrons with different substrates, turns it potentially toxic.…”

Section: Discussionmentioning

confidence: 77%

“…Thus, our investigation might set the basis for circulating Fe-loaded immune cells to be used as a prognostic marker for PD severity and, possibly, for other neurodegenerative diseases characterized by brain Fe accumulation [32,[38][39][40][41][42]. The relevance of our findings could also aid the development of future therapeutic interventions against PD.…”

Section: Introductionmentioning

confidence: 74%

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Pro-Inflammatory Priming of the Brain: The Underlying Cause of Parkinson’s Disease

Martins

Lima

Pêgo

et al. 2023

IJMS

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Parkinson’s disease (PD) is a multifactorial neurodegenerative pathology characterized by the progressive loss of dopaminergic neurons in the substantia nigra of the brain. Aging is considered the main risk factor for the development of idiopathic PD. However, immunity and inflammation play a crucial role in the pathogenesis of this disorder. In mice, we showed that pro-inflammatory priming of the brain sensitizes to severe PD development, regardless of animal age. Age-related sub-acute inflammation, as well as the activation of the immune response upon exposure to harmful stimuli, enhances PD manifestations. The severity of PD is influenced by the engagement of host resistance mechanisms against infection based on the removal of iron (Fe) from the circulation. The sequestration of Fe by immune cells prevents pathogens from proliferating. However, it leads to the formation of a Fe-loaded circulating compartment. When entering the brain through a compromised blood-brain barrier, Fe-loaded immune cells contribute to enhancing neuroinflammation and brain Fe overload. Thus, pro-inflammatory priming of the brain exacerbates neuronal damage and represents a risk factor for the development of severe PD symptoms. Further investigations are now required to better understand whether therapeutic interventions inhibiting this phenomenon might protect against PD.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 74%

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Pro-Inflammatory Priming of the Brain: The Underlying Cause of Parkinson’s Disease

Martins

Lima

Pêgo

et al. 2023

IJMS

Self Cite

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Cell Death-Osis of Dopaminergic Neurons and the Role of Iron in Parkinson's Disease

Lima

Pêgo

Barros

et al. 2021

Antioxidants & Redox Signaling

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Nutritional Strategies for Treating Iron Malnutrition: Implications on Nutrikinetic Approaches

Chekraverthy

Pardhe

Kiran

et al. 2023

Curr Res Nutr Food Sci

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Malnutrition remains a major global issue-affecting people of all ages. Iron deficiency is one of the existing malnutrition deficiencies limiting long-term human development. Food-based interventions play a vital role in the growth, development (physical and cognitive), and socioeconomic status of an individual. Several food-based approaches (viz., fortification and bio fortification of staple foods) have been employed for improving malnutrition in vulnerable populations. In underdeveloped countries, staple foods like rice, wheat, beans, and pearl millets etc. are being actively fortified and bio fortified to enhance the iron content intended to deliver the required nourishment with optimal consumption. However, translational iron levels from functional foods may not be proportional to iron absorbed into systems. Considering the effectiveness of bioavailability, additional emphasis is required in establishing the same for the functional foods which could serve as an effective alternative to existing methods in mitigating iron malnutrition. This review emphasizes the importance of iron, iron physio-pathological, and the current status of food strategies in dealing with iron malnutrition.

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Iron as Therapeutic Target in Human Diseases

Abstract: Iron is essential for almost all organisms, being involved in oxygen transport, DNA synthesis, and respiration; however, it is also potentially toxic via the formation of free radicals [...]

Cited by 4 publications

References 50 publications

Pro-Inflammatory Priming of the Brain: The Underlying Cause of Parkinson’s Disease

Pro-Inflammatory Priming of the Brain: The Underlying Cause of Parkinson’s Disease

Cell Death-Osis of Dopaminergic Neurons and the Role of Iron in Parkinson's Disease

Nutritional Strategies for Treating Iron Malnutrition: Implications on Nutrikinetic Approaches

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