scholarly journals Biochemical and Structural Characteristics, Gene Regulation, Physiological, Pathological and Clinical Features of Lipocalin-Type Prostaglandin D2 Synthase as a Multifunctional Lipocalin

2021 ◽  
Vol 12 ◽  
Author(s):  
Yoshihiro Urade

Lipocalin-type prostaglandin (PG) D2 synthase (L-PGDS) catalyzes the isomerization of PGH2, a common precursor of the two series of PGs, to produce PGD2. PGD2 stimulates three distinct types of G protein-coupled receptors: (1) D type of prostanoid (DP) receptors involved in the regulation of sleep, pain, food intake, and others; (2) chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) receptors, in myelination of peripheral nervous system, adipocyte differentiation, inhibition of hair follicle neogenesis, and others; and (3) F type of prostanoid (FP) receptors, in dexamethasone-induced cardioprotection. L-PGDS is the same protein as β-trace, a major protein in human cerebrospinal fluid (CSF). L-PGDS exists in the central nervous system and male genital organs of various mammals, and human heart; and is secreted into the CSF, seminal plasma, and plasma, respectively. L-PGDS binds retinoic acids and retinal with high affinities (Kd < 100 nM) and diverse small lipophilic substances, such as thyroids, gangliosides, bilirubin and biliverdin, heme, NAD(P)H, and PGD2, acting as an extracellular carrier of these substances. L-PGDS also binds amyloid β peptides, prevents their fibril formation, and disaggregates amyloid β fibrils, acting as a major amyloid β chaperone in human CSF. Here, I summarize the recent progress of the research on PGD2 and L-PGDS, in terms of its “molecular properties,” “cell culture studies,” “animal experiments,” and “clinical studies,” all of which should help to understand the pathophysiological role of L-PGDS and inspire the future research of this multifunctional lipocalin.

PEDIATRICS ◽  
1966 ◽  
Vol 38 (2) ◽  
pp. 319-320 ◽  
Author(s):  
Joaquin Cravioto ◽  
Elsa R. DeLicardie ◽  
Herbert G. Birch

IN THIS MONOGRAPH we report the results of an experimental and ecologic study concerned with estimating some of the effects which malnutrition in early childhood may have upon neurointegrative functioning. In particular, we have been concerned with the association between malnutrition early in childhood and intersensory organization in children during the school years. A study of these relationships has derived from a concern with the possibility that inadequate food intake, particularly as represented by protein-calorie malnutrition, affects not only stature and weight, but also the capacity to learn. If this is indeed the case, then the significance of the observable and dramatic consequences of malnutrition for physical stature may be but one visible sign of functionally, perhaps, far more important non-visible handicapping. Findings on the effects which malnutrition has on the central nervous system suggest strongly that protein deficiency may result in structural lesions of the nervous system. Animals experimentally deprived are persistently delayed in achieving simple developmental landmarks, appear to be less adequate in environmental responsiveness and slower in learning as well as poorer in the retention of that which has been learned than normal controls. Considering the animal experiments and the findings in humans as a unit, one is led to be concerned with what in an ecologic sense could be called a "spiral" effect. A low level of adaptive capacity, ignorance, social custom, infection, or environmental paucity of foodstuffs appear to result in malnutrition which may produce a large pool of individuals who come to function in suboptimal ways.


10.1038/78682 ◽  
2000 ◽  
Vol 6 (8) ◽  
pp. 916-919 ◽  
Author(s):  
Frédérique Bard ◽  
Catherine Cannon ◽  
Robin Barbour ◽  
Rae-Lyn Burke ◽  
Dora Games ◽  
...  

2013 ◽  
Vol 154 (4) ◽  
pp. 128-135 ◽  
Author(s):  
György Csaba

The notion of the perinatal „hormonal imprinting” has been published at first in 1980 and since that time it spred expansively. The imprintig develops at the first encounter between the developing receptor and the target hormone – possibly by the alteration of the methylation pattern of DNA – and it is transmitted to the progeny generations of the cell. This is needed for the complete development of the receptor’s binding capacity. However, molecules similar to the target hormone (hormone-analogues, drugs, chemicals, environmental pollutants) can also bind to the developing receptor, causing faulty imprinting with life-long consequences. This can promote pathological conditions. Later it was cleared that in other critical periods such as puberty, imprinting also can be provoked, even in any age in differentiating cells. The central nervous system (brain) also can be mistakenly imprinted, which durably influences the dopaminergic, serotonergic and noradrenergic system and this can be manifested – in animal experiments – in alterations of the sexual and social behavior. In our modern age the faulty hormonal imprintig is inavoidable because of the mass of medicaments, chemicals, the presence of hormone-like materials (e.g. soya phytosteroids) in the food, and environmental pollutants. The author especially emphasizes the danger of oxytocin, as a perinatal imprinter, as it is used very broadly and can basically influence the emotional and social spheres and the appearance of certain diseases such as auitism, schizophrenia and parkinsonism. The danger of perinatal imprinters is growing, considering their effects on the human evolution. Orv. Hetil., 2013, 154, 128–135.


2020 ◽  
Vol 19 (1) ◽  
pp. 3-23
Author(s):  
Jianan Lu ◽  
Yujie Luo ◽  
Shuhao Mei ◽  
Yuanjian Fang ◽  
Jianmin Zhang ◽  
...  

: Melatonin is a hormone produced in and secreted by the pineal gland. Besides its role in regulating circadian rhythms, melatonin has a wide range of protective functions in the central nervous system (CNS) disorders. The mechanisms underlying this protective function are associated with the regulatory effects of melatonin on related genes and proteins. In addition to messenger ribonucleic acid (RNA) that can be translated into protein, an increasing number of non-coding RNAs in the human body are proven to participate in many diseases. This review discusses the current progress of research on the effects of melatonin modulation of non-coding RNAs (ncRNAs), including microRNA, long ncRNA, and circular RNA. The role of melatonin in regulating common pathological mechanisms through these ncRNAs is also summarized. Furthermore, the ncRNAs, currently shown to be involved in melatonin signaling in CNS diseases, are discussed. The information compiled in this review will open new avenues for future research into melatonin mechanisms and provide a further understanding of ncRNAs in the CNS.


2021 ◽  
Vol 22 (18) ◽  
pp. 10028
Author(s):  
Julia Doroszkiewicz ◽  
Magdalena Groblewska ◽  
Barbara Mroczko

The gut microbiome has attracted increasing attention from researchers in recent years. The microbiota can have a specific and complex cross-talk with the host, particularly with the central nervous system (CNS), creating the so-called “gut–brain axis”. Communication between the gut, intestinal microbiota, and the brain involves the secretion of various metabolites such as short-chain fatty acids (SCFAs), structural components of bacteria, and signaling molecules. Moreover, an imbalance in the gut microbiota composition modulates the immune system and function of tissue barriers such as the blood–brain barrier (BBB). Therefore, the aim of this literature review is to describe how the gut–brain interplay may contribute to the development of various neurological disorders, combining the fields of gastroenterology and neuroscience. We present recent findings concerning the effect of the altered microbiota on neurodegeneration and neuroinflammation, including Alzheimer’s and Parkinson’s diseases, as well as multiple sclerosis. Moreover, the impact of the pathological shift in the microbiome on selected neuropsychological disorders, i.e., major depressive disorders (MDD) and autism spectrum disorder (ASD), is also discussed. Future research on the effect of balanced gut microbiota composition on the gut–brain axis would help to identify new potential opportunities for therapeutic interventions in the presented diseases.


2018 ◽  
Vol 13 (3-4) ◽  
pp. 70-75
Author(s):  
M.V. Khaitovych

Relevance. Anti-depressant effects of NMDA receptor antagonists have been proven, a close association between low levels of magnesium in the blood and depression. Therefore, in recent years, antidepressant properties of magnesium are actively studied in animal experiments. Objective: To review modern literary sources about the role of magnesium deficiency in the pathogenesis of diseases of the central nervous system. Materials and methods. Searching for a depth of 12 years at Scopus, Google Scholar. Results. The results of experimental and clinical researches pointed out on association between low level of magnesium in hair, liquor, brain with higher risk of development dementia, depression and anxiety. An additional supplementation with magnesium in patients associates with decreasing risk of ischemic stroke and dementia, in pregnancy – provides neuroprotection of fetus, in case of depression increases effectiveness of antidepressants, in brain injury associates with faster recovery of cognitive functions, in migraines - with decreasing in the frequency of attacks and improvement of the quality patients’ lives, in case of neuroleptic therapy - with the possibility of delayed appearance or absence of manifestations of drug parkinsonism. These changes are explained by antagonistic effects of magnesium on glutamate receptors, decreasing oxidative stress intensity as well as neural cell  apoptosis. Conclusion. Magnesium plays an important neuroprotective role.


Author(s):  
Ulrike Schrifl ◽  
SakkuBai Naidu ◽  
Ali Fatemi

The term “leukodystrophies” refers to a group of genetic diseases characterized by degeneration of white matter in the central nervous system. Depending on the type of leukodystrophy, the phenotype can range from early infantile-onset, rapid, progressive forms to adult-onset slowly progressive variants. The understanding, definition, and classification have been enhanced greatly by the combined use of neuroimaging, especially MRI, and genetic techniques. The window for targeted therapeutic interventions remains brief and management is often limited to symptomatic, supportive, and palliative care, and new approaches for treatment remain a great task for future research.


2020 ◽  
Vol 21 (23) ◽  
pp. 8941
Author(s):  
Seunghyuk Choi ◽  
Dae Ki Hong ◽  
Bo Young Choi ◽  
Sang Won Suh

Zinc is a trace metal ion in the central nervous system that plays important biological roles, such as in catalysis, structure, and regulation. It contributes to antioxidant function and the proper functioning of the immune system. In view of these characteristics of zinc, it plays an important role in neurophysiology, which leads to cell growth and cell proliferation. However, after brain disease, excessively released and accumulated zinc ions cause neurotoxic damage to postsynaptic neurons. On the other hand, zinc deficiency induces degeneration and cognitive decline disorders, such as increased neuronal death and decreased learning and memory. Given the importance of balance in this context, zinc is a biological component that plays an important physiological role in the central nervous system, but a pathophysiological role in major neurological disorders. In this review, we focus on the multiple roles of zinc in the brain.


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