Brain iron transport Qian, Zhong‐Ming; Ke, Ya
Biological reviews of the Cambridge Philosophical Society,
October 2019, 2019-10-00, 20191001, Letnik:
94, Številka:
5
Journal Article
Recenzirano
ABSTRACT
Brain iron is a crucial participant and regulator of normal physiological activity. However, excess iron is involved in the formation of free radicals, and has been associated with oxidative ...damage to neuronal and other brain cells. Abnormally high brain iron levels have been observed in various neurodegenerative diseases, including neurodegeneration with brain iron accumulation, Alzheimer's disease, Parkinson's disease and Huntington's disease. However, the key question of why iron levels increase in the relevant regions of the brain remains to be answered. A full understanding of the homeostatic mechanisms involved in brain iron transport and metabolism is therefore critical not only for elucidating the pathophysiological mechanisms responsible for excess iron accumulation in the brain but also for developing pharmacological interventions to disrupt the chain of pathological events occurring in these neurodegenerative diseases. Numerous studies have been conducted, but to date no effort to synthesize these studies and ideas into a systematic and coherent summary has been made, especially concerning iron transport across the luminal (apical) membrane of the capillary endothelium and the membranes of different brain cell types. Herein, we review key findings on brain iron transport, highlighting the mechanisms involved in iron transport across the luminal (apical) as well as the abluminal (basal) membrane of the blood–brain barrier, the blood–cerebrospinal fluid barrier, and iron uptake and release in neurons, oligodendrocytes, astrocytes and microglia within the brain. We offer suggestions for addressing the many important gaps in our understanding of this important topic, and provide new insights into the potential causes of abnormally increased iron levels in regions of the brain in neurodegenerative disorders.
Utilizing pyridine catalysis, we developed a visible‐light‐induced transition‐metal‐free radical borylation reaction of unactivated alkyl bromides that features a broad substrate scope and mild ...reaction conditions. Mechanistic studies revealed a novel nucleophilic substitution/photoinduced radical formation pathway, which could be utilized to trigger a variety of radical processes.
To B or not to Br: A visible‐light‐induced organocatalytic borylation reaction of unactivated alkyl bromides was developed. This reaction exhibits a broad substrate scope, and mechanistic studies revealed a novel nucleophilic substitution/photoinduced radical formation pathway.
We propose a new neutron-capture site in early metal-poor and metal-free stars of ∼20-30 M that results from proton ingestion in the He shell during late stages of the stars' lives. Most of the ...neutron capture occurs in the first 106 s following proton ingestion when 13C( , n)16O produces neutron densities typical of the intermediate neutron-capture process. This phase may be followed by another lasting 107 s with 17O( , n)20Ne producing much lower neutron densities typical of the slow neutron-capture process. We explore the dependence of the proposed neutron-capture nucleosynthesis on the amount and time of proton ingestion, the initial metallicity, and the ensuing supernova shock. We obtain a range of heavy-element abundance patterns, including those attributed to the slow neutron-capture process or a combination of the slow and rapid neutron-capture processes. Our results can account for the observed ubiquity of heavy elements such as Sr and Ba in the early Galaxy and explain puzzling abundance patterns of these elements in at least some very metal-poor (VMP) stars, including those of the carbon-enhanced varieties. In the latter case, the explanation by the single site proposed here differs from the existing paradigm that attributes various classes of VMP stars to enrichment by multiple different sites.
Abnormally high brain iron, resulting from the disrupted expression or function of proteins involved in iron metabolism in the brain, is an initial cause of neuronal death in neuroferritinopathy and ...aceruloplasminemia, and also plays a causative role in at least some of the other neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Friedreich's ataxia. As such, iron is believed to be a novel target for pharmacological intervention in these disorders. Reducing iron toward normal levels or hampering the increases in iron associated with age in the brain is a promising therapeutic strategy for all iron‐related neurodegenerative disorders. Hepcidin is a crucial regulator of iron homeostasis in the brain. Recent studies have suggested that upregulating brain hepcidin levels can significantly reduce brain iron content through the regulation of iron transport protein expression in the blood‐brain barrier and in neurons and astrocytes. In this review, we focus on the discussion of the therapeutic potential of hepcidin in iron‐associated neurodegenerative diseases and also provide a systematic overview of recent research progress on how misregulated brain iron metabolism is involved in the development of multiple neurodegenerative disorders.
The wind driven by the intense neutrino emission from a protoneutron star (PNS) is an important site for producing nuclei heavier than the Fe group. Because of certain features in the neutrino ...angular distributions, the so-called fast flavor oscillations may occur very close to the PNS surface, effectively resetting the neutrino luminosities and energy spectra that drive the wind. Using the unoscillated neutrino emission characteristics from two core-collapse supernova simulations representative of relevant progenitors at the lower and higher mass end, we study the potential effects of fast flavor oscillations on neutrino-driven winds and their nucleosynthesis. We find that such oscillations can increase the total mass loss by factors up to ∼1.5-1.7 and lead to significantly more proton-rich conditions. The latter effect can greatly enhance the production of 64Zn and the so-called light p-nuclei 74Se, 78Kr, and 84Sr. Implications for abundances in metal-poor stars, Galactic chemical evolution in general, and isotopic anomalies in meteorites are discussed.
We present a method to find the stationary solutions for fast flavor oscillations of a homogeneous dense neutrino gas. These solutions correspond to collective precession of all neutrino polarization ...vectors around a fixed axis in the flavor space on average, and are conveniently studied in the co-rotating frame. We show that these solutions can account for the numerical results of explicit evolution calculations, and that even with the simplest assumption of adiabatic evolution, they can provide the average survival probabilities to good approximation. We also discuss improvement of these solutions and their use as estimates of the effects of fast oscillations in astrophysical environments.
Iron metabolism and atherosclerosis Guo, Qian; Qian, Christopher; Qian, Zhong-Ming
Trends in endocrinology and metabolism,
July 2023, 2023-07-00, 20230701, Letnik:
34, Številka:
7
Journal Article
Recenzirano
The fact that hereditary hemochromatosis (HH) patients do not show any increased incidence of atherosclerosis is often cited as the most convincing evidence against the role of iron in ...atherosclerosis.The key question about whether atherosclerosis occurs is whether there is excess iron accumulation in the artery wall, the actual location of atherosclerosis.An increase in atherosclerosis should not be observed in HH because the iron homeostasis of the arterial wall in HH is not affected.Iron content in the aortic tissue was not significantly affected in those animal studies that reported the conflicting results against iron’s role in atherogenesis.The reviewed findings, discussion, and analysis strongly suggest a causal link between iron and atherosclerosis.
Despite several decades of study, whether iron is involved in the development of atherosclerosis remains a controversial and unresolved issue. Here, we focus on the up-to-date advances in studies on role of iron in atherosclerosis and discuss possible reasons why patients with hereditary hemochromatosis (HH) do not show any increased incidence of atherosclerosis. In addition, we analyze conflicting results concerning the role of iron in atherogenesis from several epidemiological and animal studies. We argue that atherosclerosis is not observed in HH because iron homeostasis in the arterial wall, the actual location of atherosclerosis, is not significantly affected, and support a causal link between iron in the arterial wall and atherosclerosis.
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