Histamine Phosphate In principle an ideal Fenton reaction el

In principle, an ideal Fenton reaction element should have multiple oxidation states to form a redox cycle in the process of H2O2 decomposition to HO•. Although iron is very effective in catalyzing Fenton reaction, it requires a low pH value (pH 2-4) to reach the optimal catalytic efficiency, which is normally unavailable in the cellular context. Therefore, many non-ferrous elements with multiple oxidation states, such as the Mnx+/Mnx+1, Cu+/Cu2+, Al0/Al3+, Co2+/Co3+, Ce3+/Ce4+, Ruy+/Ruy+1, and Cr3+/Cr6+, have been investigated as highly efficient Fenton reaction reagents that can act under a biologically relevant pH (Fig. 7) [34]. Hence, the concept of ferroptosis could be extended as a type of cell death caused by an excess of various polyvalent metals beyond iron.
Acknowledgments This work was supported by the National Key Research and Development Program of China (No. 2016YFA0203600), the National Natural Science Foundation of China (Nos. 31822019, 91859116 and 51703195), the Fundamental Research Funds for the Central Universities (No. 2018QNA7020), the One Belt and One Road International Cooperation Project from Key Research and Development Program of Zhejiang Province (No. 2019C04024).
Introduction Iron is the most abundant transition metal on Earth and essential for life. Iron availability in primordial oceans allowed for its incorporation in living organisms. Metabolic processes catalysed by iron or by iron-sulfur clusters may be among the first of such processes to evolve on Earth and essential for the emergence of carbon-based life [22], [214]. The photolysis of water by photosynthesis around 2.45 billion years ago introduced a new global poison i.e. oxygen, causing what is described as the Great Oxygenation Event [191]. The resultant oxidising environment transformed iron into a limiting factor for life processes due to the limited solubility of the oxidised iron cation. The Histamine Phosphate is a major organ where iron accumulates with age, especially in regions of pathological relevance. The study of monogenic genetic disorders that affect iron homeostasis, and indications from dietary studies, have established that brain iron homeostasis is mostly independent of systemic iron homeostasis [15]. Furthermore, indicators of systemic iron levels weakly correlate with iron in the brain. Several neurodegenerative conditions including Alzheimer's disease (AD) and Parkinson's disease (PD) are associated with increased iron levels in affected region of the brain with levels of iron corresponding to disease severity [15]. However, the iron-mediated events that may promote neurodegeneration appear to be more intricate than iron-associated oxidative damage. Here we review the development of the “iron-hypothesis” of neurodegeneration, shifting our focus beyond iron toxicity to consider the recently (re)discovered iron-dependent programmed cell death pathway called ferroptosis.
Iron homeostasis in the brain
Role of iron in neurodegeneration Iron is essential for normal brain development and cognitive function. The deficiency of iron thus adversely impacts on neurological development and function, especially in prenatal or early postnatal stages, where the dysfunction may affect memory and learning ability [171]. Iron progressively accumulates in the brain with age with a greater accumulation observed in the cortex and the nuclei of the basal ganglia viz. SN, putamen, globus pallidus and caudate nucleus; iron accumulation in these regions is associated with neurodegenerative disorders [15]. Neurodegenerative disorders that are associated with high brain-iron include AD, PD, HD, MND/ALS, infantile neuroaxonal dystrophy (INAD), Schindler disease, and other neuroaxonal dystrophies termed NBIA disorders [15], [74], [96], [154], [216]. Further, iron overload is associated with a subset of psychiatric diseases [44], [71], [97]. While the deleterious effects of enhanced iron in the brain have been ascribed to an oxidative damage component, the recently (re)discovered iron-mediated regulated cell death pathway, ferroptosis, is now under scrutiny for its role in neurodegeneration and cognitive impairment.