Frontiers in Neuroendocrinology, Год журнала: 2023, Номер 72, С. 101113 - 101113
Опубликована: Ноя. 21, 2023
Язык: Английский
Physiological Research, Год журнала: 2023, Номер unknown, С. S317 - S322
Опубликована: Дек. 17, 2023
While there are hundreds of synthetic steroids conjugates with acids, sugars, proteins and other molecules, only two types occur in living organisms, namely sulfates glucuronides. Steroid glucuronidation the human liver is main mechanism controlling levels biological activity unconjugated hormones, glucuronides their excretion products. This process generally irreversible. On hand, possess own that differs from steroid, emphasizing importance steroid sulfatases sulfotransferases. Due to negative charge, cannot cross blood-cell barrier have use transporters. Their efflux mediated by specific transporters ATP binding cassette protein group, which thus further factors physiological effects. sulfates, especially dehydroepiandrosterone sulfate (DHEAS) neuroactive steroids, well-known effects as allosteric modulators some neurotransmitter receptors, functioning ion channels, such gamma-aminobutyric acid, type A (GABAA) receptors or N-methyl-D-aspartate (NMDA) receptors. In this minireview, we highlight recent findings non-genomic actions through G-protein coupled (GPCR), believe show way research. few studies even indicated DHEAS may indirectly regulate gene expression via ligand membrane receptor and, second messenger formation, activate like cAMP Regulated Elements Binding (CREB), then binds regulated DNA elements expressed gene, a ”classical“ genomic effect.
Язык: Английский
Процитировано
6
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7106 - 7106
Опубликована: Июнь 28, 2024
Peroxisome proliferator-activated receptors (PPARs) may play an important role in the pathomechanism/pathogenesis of Alzheimer's disease (AD) and several other neurological/neuropsychiatric disorders. AD leads to progressive alterations redox state, ion homeostasis, lipids, protein metabolism. Significant molecular processes functioning signaling pathways result degeneration death synapses neuronal cells, leading most severe dementia. receptor alpha (PPAR-α) is among affected by AD; it regulates transcription genes related metabolism cholesterol, fatty acids, lipids neurotransmission, mitochondria biogenesis, function. PPAR-α involved cholesterol transport mitochondria, substrate for neurosteroid biosynthesis. PPAR-α-coding enzymes, such as sulfotransferases, which are responsible sulfation. The relation between cholesterol/neurosteroids have a significant impact on course progression neurodegeneration/neuroprotection processes. Unfortunately, despite many years intensive studies, pathogenesis unknown therapy neurodegenerative diseases symptomatic, presenting goal challenge today. This review presents recent achievements therapeutic approaches AD, targeting its neurosteroids neuropsychiatric
Язык: Английский
Процитировано
2
The Journal of Steroid Biochemistry and Molecular Biology, Год журнала: 2023, Номер 232, С. 106353 - 106353
Опубликована: Июнь 17, 2023
A central part of human sulfation pathways is the spatially and temporally controlled desulfation biologically highly potent steroid hormones. The responsible enzyme - sulfatase (STS) expressed in placenta peripheral tissues, such as fat, colon, brain. shape this its mechanism are probably unique biochemistry. STS was believed to be a transmembrane protein, spanning Golgi double-membrane by stem region formed two extended internal alpha-helices. New crystallographic data however challenge view. now portraited trimeric membrane-associated complex. We discuss impact these results on function general we hypothesis that new structural understanding suggests product inhibition regulator enzymatic activity.
Язык: Английский
Процитировано
5
Genes Brain & Behavior, Год журнала: 2024, Номер 23(3)
Опубликована: Май 5, 2024
Abstract Steroid sulphatase (STS) cleaves sulphate groups from steroid hormones, and (sulphate) levels correlate with mood age‐related cognitive decline. In animals, STS inhibition or deletion of the associated gene, enhances memory/neuroprotection alters hippocampal neurochemistry. Little is known about consequences constitutive deficiency on memory‐related processes in humans. We investigated self‐reported memory performance (Multifactorial Memory Questionnaire), word‐picture recall recent (Kessler Psychological Distress Scale, K10) adult males diagnosed dermatological condition X‐linked ichthyosis (XLI; n = 41) female carriers XLI‐associated genetic variants ( 79); we compared results to those obtained matched control subjects [diagnosed vulgaris (IV, 98) recruited general population 250)]. Using UK Biobank, mood/memory‐related neuroanatomy deletions encompassing 28) non‐carriers 34,522). found poorer lower perceived abilities XLI groups. variant individuals IV reported more adverse symptoms, reduced contentment greater use aids, controls. Mood findings appeared largely independent. Neuroanatomical analysis only indicated a nominally‐significantly larger molecular layer right body relative non‐carriers. humans, appears mood‐independent impairments but not large effects underlying brain structure; mediating psychobiological mechanisms might be explored further new mammalian models lacking developmentally.
Язык: Английский
Процитировано
1
Gene, Год журнала: 2024, Номер 927, С. 148700 - 148700
Опубликована: Июнь 15, 2024
Язык: Английский
Процитировано
1
Essays in Biochemistry, Год журнала: 2024, Номер unknown
Опубликована: Июль 12, 2024
Abstract Sulfatase (STS) and sulfotransferases (SULT) have important role in the biosynthesis action of steroid hormones. STS catalyzes hydrolysis estrone-sulfate (E1-S) dehydroepiandrosterone-sulfate (DHEA-S), while catalyze reverse reaction require 3-phosphoadenosine-5-phosphosulfate as a sulfate donor. These enzymes control concentration active estrogens androgens peripheral tissues. Aberant expression SULT genes has been found both, benign hormone-dependent diseases cancers. The aim this review is to present current knowledge on gynecological cancers, endometrial (EC) ovarian cancer (OC). EC most common OC lethal cancer. cancers primarily affect postmenopausal women therefore rely local production hormones from inactive precursors, either DHEA-S or E1-S. Following cellular uptake by organic anion transporting polypeptides (OATP) transporters (OAT), regulate formation androgens, thus disturbed balance between can contribute onset progression importance these estrogen long recognized, provides new data their regulation inhibition, potential prognostic biomarkers.
Язык: Английский
Процитировано
1
RSC Advances, Год журнала: 2024, Номер 14(49), С. 36352 - 36369
Опубликована: Янв. 1, 2024
Photoaffinity labels (PALs) for sulfated steroid binding sites on GABA A and NMDA receptors. The PALs have varying profiles of positive negative modulatory (PAM NAM) actions.
Язык: Английский
Процитировано
1
Biomolecules, Год журнала: 2023, Номер 13(2), С. 383 - 383
Опубликована: Фев. 17, 2023
The emergence of metabolomics and quantification approaches is revealing new biomarkers applied to drug discovery. In this context, tandem mass spectrometry the method choice, requiring a specific validation process for preclinical clinical applications. Research on two classes lipid mediators, steroids cannabinoids, has revealed potential interaction in cannabis addiction metabolism-related disorders. Here we present development GC-MS/MS LC-MS/MS methods routine targeted respectively. were developed using an isotopic approach, including linearity, selectivity, LLOQ determination, matrix effect, carryover, between- within-run accuracy precision, stability tests measure 11 seven cannabinoids human plasma. These satisfactory most validity conditions, although not all met acceptance criteria analytes. A comparison calibration curves biological surrogate matrices methanol showed that latter condition was more applicable our endogenous compounds. conclusion, GLP-qualified rather than GLP-validated methods, which can be used analytical studies dedicated purposes, by combining appropriate system suitability testing, quality controls matrix.
Язык: Английский
Процитировано
3
CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 30(2)
Опубликована: Авг. 21, 2023
Abstract Background Alzheimer's disease (AD) is one of the most common neurodegenerative diseases leading to dementia in elderly people. Microglia‐mediated neuroinflammation plays an important role AD pathogenesis, so modulation has emerged as essential therapeutic method improve AD. The current study aims investigate whether MKP‐1 can regulate microglia phenotype and inflammatory factor release explore its possible mechanisms. Methods Amyloid precursor protein/PS1 double transgenic mice wild‐type were selected locations amyloid‐β (Aβ) plaques different regions brains. Changes detected using model cells. factors within immortalized BV2 murine investigated by regulating expression MKP‐1. Results distribution Aβ brain was region‐specific. downregulated mice, vitro, with increasing concentrations, reduced. over‐expression increased M2 but decreased M1 accompanied changes inhibition yielded opposite result. Conclusion regulated through p38 signaling pathway.
Язык: Английский
Процитировано
2
Hormones and Behavior, Год журнала: 2022, Номер 147, С. 105281 - 105281
Опубликована: Ноя. 24, 2022
Язык: Английский
Процитировано
3