Iron Targeting Therapies Study

Creative Biolabs has over 10 years of experience in neuroscience and we have successfully established a comprehensive platform. With our advanced platform and professional team, Creative Biolabs is willing to provide customized services such as animal model establishment and iron chelator detection to solve the challenges of your projects in Parkinson's disease (PD) mechanism exploration.

Crucial Roles of Iron

It is well known that iron is a vital trace element that is necessary for the normal metabolism of the central nervous system. Iron is closely linked to many important processes, such as oxygen transport, mitochondrial respiration, oxidative phosphorylation, DNA synthesis, myelination, and neurotransmitter synthesis and metabolism. Abnormal iron homeostasis can generate free radicals that cause cellular damage. In addition, during aging, various iron complexes accumulate in brain regions associated with motor and cognitive impairment. Importantly, in various neurodegenerative diseases, such as Alzheimer's disease (AD) and PD, changes in iron homeostasis cause alterations in intracellular iron distribution and accumulation.

Iron and PD

PD is a common neurological disease, and its pathogenesis is closely related to environmental and genetic factors. Iron accumulates in the brain during normal aging, but triples in specific brain regions in PD. Evidence suggests that long-term exposure to heavy metals such as iron, lead, and manganese may increase the risk of PD because of their possible accumulation and oxidative stress in the substantia nigra. In addition, studies have found that abnormal iron metabolism is associated with PD, with increased iron load found in the pathologically affected areas of PD. This increase in iron concentration exceeds the iron-buffering capacity of specific complexes and unbound excess cellular iron may be cytotoxic and induce neurotoxicity through the generation of reactive oxygen species (ROS).

Iron Targeting Therapies for PD

Tight regulation of iron metabolism facilitates the availability of iron for biochemical functions while reducing iron involvement in the formation of harmful free radicals. The iron load in the PD brain is increased, and thus, strategies to remove excess iron using iron chelation to treat PD have attracted widespread attention. An attractive approach to eliminating iron accumulation is to provide neuroprotection with iron chelators that can cross the blood-brain barrier and reduce excess iron accumulation. Studies in animal models of PD have demonstrated the therapeutic effect of iron chelators, which can cross the blood-brain barrier, reduce intraneuronal iron and reduce ROS formation, thereby increasing neuronal survival. In short, evaluating the pathophysiological role of iron in PD by chelation is a very promising strategy, which can reduce oxidative damage associated with local iron deposition without affecting circulating metals.

Fig.1 Ferroptosis as a therapeutic target in PD. (Devos, et al., 2020)

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Reference

1. Devos, D.; et al. Conservative iron chelation for neurodegenerative diseases such as Parkinson's disease and amyotrophic lateral sclerosis. Journal of Neural Transmission. 2020, 127(2): 189-203.