Frontiers in Neuroendocrinology, Journal Year: 2023, Volume and Issue: 72, P. 101113 - 101113
Published: Nov. 21, 2023
Language: Английский
Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 149, P. 105191 - 105191
Published: April 20, 2023
Endogenous neurosteroids and synthetic neuroactive steroids (NAS) are important targets for therapeutic development in neuropsychiatric disorders. These modulate major signaling systems the brain intracellular processes including inflammation, cellular stress autophagy. In this review, we describe studies performed using unnatural enantiomers of key neurosteroids, which physiochemically identical to their natural counterparts except rotation polarized light. led insights how NAS interact with receptors, ion channels sites action. Certain effects show high enantioselectivity, consistent actions chiral environments likely direct interactions proteins. Other no enantioselectivity even reverse enantioselectivity. The spectrum raises possibility that these agents, once considered only as tools preclinical studies, have potential complements some cases may exceed counterparts. Here review from perspective novel neurotherapeutics.
Language: Английский
Citations
20
Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14
Published: July 4, 2023
While estrogens are well known for their pivotal role in the female reproductive system, they also play a crucial function regulating physiological processes associated with learning and memory brain. Moreover, have neuroprotective effects pathogenesis of Alzheimer's disease (AD). Importantly, AD has higher incidence older postmenopausal women than men, estrogen treatment might reduce risk these women. In general, bind to activate receptors (ERs)-mediated transcriptional machineries, stimulate signal transduction through membrane ERs (mERs). Estrogen-related (ERRs), which share homologous sequences but lack estrogen-binding capabilities, widely highly expressed human brain been implicated pathogenesis. this review, we primarily provide summary ER ERR expression patterns addition, summarize recent studies on memory. We then review discuss research that elucidated functions importance ERRs pathogenesis, including Aβ clearance reduction phosphorylated tau levels. Elucidation mechanisms underlying ER- ERR-mediated machineries healthy diseased brains would new perspectives diagnosis AD. Furthermore, exploring potential receptors, ERs, will facilitate better understanding sex differences observed AD, lead novel sex-specific therapeutic approaches.
Language: Английский
Citations
18
Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(4), P. 101480 - 101480
Published: March 22, 2024
The gut microbiome is associated with pathological neurophysiological evolvement in extremely premature infants suffering from brain injury. exact underlying mechanism and its metabolic signatures are not fully understood. To decipher metabolite profiles linked to neonatal injury, we investigate the fecal plasma metabolome of samples obtained a cohort 51 at several time points, using liquid chromatography (LC)-high-resolution mass spectrometry (MS)-based untargeted metabolomics LC-MS/MS-based targeted analysis for investigating bile acids amidated acid conjugates. data integrated 16S rRNA gene amplicon as well patient cytokine, growth factor, T cell profiles. We find an early onset differentiation neuroactive metabolites between without detect bacterially derived amino conjugates feces. These results provide insights into early-life infants.
Language: Английский
Citations
8
Heliyon, Journal Year: 2024, Volume and Issue: 10(15), P. e35562 - e35562
Published: Aug. 1, 2024
The blood-brain interface poses formidable obstacles in addressing neurological conditions such as Alzheimer's, Multiple Sclerosis, brain cancers, and cerebrovascular accidents. Serving a safeguard against potential threats the blood, this barrier hinders direct drug delivery to affected cells, necessitating specialized transport mechanisms. Within realm of nanotechnology, creation nanoscale carriers, including macromolecules polymers, lipids, metallic nanoparticles, is gaining prominence. These tailored diverse forms sizes enriched with specific functional groups for enhanced penetration targeting, are capturing growing interest. This revised abstract explores macromolecular dimension understanding how nanoparticles interact barrier. It re-evaluates structure function barrier, highlighting nanocarriers utilized brain. discussion delves into intricate pathways through which drugs navigate emphasizing distinctive attributes nanocarriers. Additionally, it recent innovations nanotechnology unconventional approaches delivery. Ultimately, paper addresses intricacies considerations developing macromolecular-based nanomedicines brain, aiming advance evolution ailments.
Language: Английский
Citations
4
Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 60(8), P. 4373 - 4395
Published: April 25, 2023
Abstract Hair is a noninvasive valuable biospecimen for the long-term assessment of endogenous metabolic disturbance. Whether hair suitable identifying biomarkers Alzheimer’s disease (AD) process remains unknown. We aim to investigate metabolism changes in after β-amyloid (Aβ 1-42 ) exposure rats using ultra-high-performance liquid chromatography-high-resolution mass spectrometry–based untargeted and targeted methods. Thirty-five days Aβ induction, displayed significant cognitive deficits, forty metabolites were changed, which twenty belonged three perturbed pathways: (1) phenylalanine phenylalanine, tyrosine, tryptophan biosynthesis— l -phenylalanine, phenylpyruvate, ortho-hydroxyphenylacetic acid, phenyllactic acid are up-regulated; (2) arachidonic (ARA) metabolism—leukotriene B4 (LTB4), arachidonyl carnitine, 5(S)-HPETE upregulation, but ARA, 14,15-DiHETrE, 5(S)-HETE, PGB2 opposite; (3) unsaturated fatty eicosapentaenoic (EPA), docosahexaenoic (DHA), FA 18:3 + 1O, 2O downregulated. Linoleic belonging biosynthesis includes upregulation 8-hydroxy-9,10-epoxystearic 13-oxoODE, 18:2 4O, downregulation 9(S)-HPODE dihomo-γ-linolenic acid. In addition, cortisone dehydroepiandrosterone steroid hormone upregulated. These pathways also correlate with impairment stimulation. Furthermore, DHA, EPA, have been previously implicated cerebrospinal fluid AD patients show similar changing trend rats’ hair. data suggest can be useful that well reflects expression non-polar molecules under stimulation, five potential serve as novel biomarkers.
Language: Английский
Citations
10
Steroids, Journal Year: 2023, Volume and Issue: 201, P. 109335 - 109335
Published: Nov. 10, 2023
Language: Английский
Citations
10
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 14, 2025
Following SARS-CoV-2 infection, ∼10-35% of COVID-19 patients experience long COVID (LC), in which often debilitating symptoms persist for at least three months. Elucidating the biologic underpinnings LC could identify therapeutic opportunities. We utilized machine learning methods on analytes and patient reported outcome surveys provided over 12 months after hospital discharge from >500 hospitalized IMPACC cohort to a multi-omics "recovery factor". participants who experienced had lower recovery factor scores compared without LC. Biologic characterization revealed increased levels plasma proteins associated with inflammation, elevated transcriptional signatures heme metabolism, decreased androgenic steroids patients. The was also altered circulating immune cell frequencies. Notably, were predictive occurrence as early admission, irrespective acute disease severity. Thus, identifies risk infection reveals biomarkers potential treatment targets.
Language: Английский
Citations
0
Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 179 - 179
Published: March 6, 2025
Background/Objectives: Prenatal depression (PND) poses a significant threat to the health of both mother and developing fetus. Despite its increasing prevalence, pathophysiology PND is not yet fully elucidated. Methods: In this study, we aimed investigate fecal metabolites gut microbiota in patients compared healthy controls explore potential correlations between these factors. Results: Through untargeted metabolomics analysis, identified 75 significantly altered patients, which 27 were structurally annotated implicated key pathways, such as linoleic acid metabolism phenylalanine, tyrosine, tryptophan biosynthesis. Notably, two Clostridia-associated enterobacteria, unclassified_c_Clostridia unclassified_f_Lachnospiraceae, enriched group, positively correlated with tyrosine negatively multiple sulfated neurosteroids. Conclusions: Our findings underscore robust association dysbiosis metabolic disturbances PND, specific alterations noted metabolism, neurosteroid homeostasis, pathways. These dysregulated metabolites-tyrosine, neurosteroids, acid-may serve diagnostic biomarkers therapeutic targets. Moreover, their interplay provides new insights into pathophysiological mechanisms particularly highlighting role gut-brain axis signaling neuroendocrine dysregulation inflammatory responses. However, further large-scale studies animal models are required validate detailed mechanistic
Language: Английский
Citations
0
Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 646 - 646
Published: April 30, 2025
Cholesterol sulfate (CS) is a naturally occurring cholesterol derivative that widely distributed across various tissues and body fluids. In humans, its biosynthesis primarily mediated by the sulfotransferase (SULT) 2B1b (SULT2B1b). Over years, CS has been found to play critical roles in physiological processes, including epidermal cell adhesion, sperm capacitation, platelet coagulation, glucolipid metabolism, bone gut microbiota neurosteroid biosynthesis, T-cell receptor signaling, immune migration. this review, we first introduce endogenous regulation of metabolism. We then highlight current advances understanding CS. Finally, delve into implications diseases, with particular focus on mechanism action potential therapeutic applications. A comprehensive CS’s function, regulation, role as disease modifier offers novel insights could pave way for innovative strategies targeting wide range conditions.
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7106 - 7106
Published: June 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
Language: Английский
Citations
2