N-methyl-D-aspartate receptors (NMDARs) play vital roles in normal brain functions (i.e., learning, memory, and neuronal development) and various neuropathological conditions, such as epilepsy, autism, Parkinson's disease, Alzheimer's disease, and traumatic brain injury. Endogenous neuroactive steroids such as 24(S)-hydroxycholesterol (24(S)-HC) have been shown to influence NMDAR activity, and positive allosteric modulators (PAMs) derived from 24(S)-hydroxycholesterol scaffold can also enhance NMDAR function. This study describes the structural determinants and mechanism of action for 24(S)-hydroxycholesterol and two novel synthetic analogs (SGE-550 and SGE-301) on NMDAR function. We also show that these agents can mitigate the altered function caused by a set of loss-of-function missense variants in NMDAR GluN subunit-encoding GRIN genes associated with neurological and neuropsychiatric disorders. We anticipate that the evaluation of novel neuroactive steroid NMDAR PAMs may catalyze the development of new treatment strategies for GRIN-related neuropsychiatric conditions.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644378 | PMC |
| http://dx.doi.org/10.1007/s00018-022-04667-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identification of miRNAs Involved in Olfactory Regulation in Antennae of Beet Webworm, (Lepidoptera: Pyralidae).
Life (Basel)
December 2024
Key Laboratory of Biohazard Monitoring, Green Prevention and Control for Artificial Grassland, Ministry of Agriculture and Rural Affairs, Institute of Grassland Research of Chinese Academy of Agricultural Sciences, Hohhot 010010, China.
The beet webworm, , is a typical migratory pest. Although miRNAs participate in many physiological functions, little is known about the functions of miRNAs in olfactory regulation. In this study, 1120 (869 known and 251 novel) miRNAs were identified in the antennae of by using high-throughput sequencing technology.
View Article and Find Full Text PDFIntegration of network toxicology and transcriptomics reveals the novel neurotoxic mechanisms of 2, 2', 4, 4'-tetrabromodiphenyl ether.
J Hazard Mater
December 2024
Department of Occupational and Environmental Health, MOE Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:
The brominated flame retardant 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) is known as a developmental neurotoxicant, yet the underlying mechanisms remain unclear. This study aims to explore its neurotoxic mechanisms by integrating network toxicology with transcriptomics based on human neural precursor cells (hNPCs) and neuron-like PC12 cells. Network toxicology revealed that PBDE-47 crosses the blood-brain barrier more effectively than heavier PBDE congeners, and is associated with disruptions in 159 biological pathways, including cytosolic DNA-sensing pathway, ferroptosis, cellular senescence, and chemokine signaling pathway.
View Article and Find Full Text PDFDevelopment and application of a predictive model for survival and drug therapy based on COVID-19-related lncRNAs in non-small cell lung cancer.
Medicine (Baltimore)
December 2024
Department of Clinical Laboratory, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, China.
Numerous studies have substantiated the pivotal role of long non-coding RNAs (lncRNAs) in the progression of non-small cell lung cancer (NSCLC) and the prognosis of afflicted patients. Notably, individuals with NSCLC may exhibit heightened vulnerability to the novel coronavirus disease (COVID-19), resulting in a more unfavorable prognosis subsequent to infection. Nevertheless, the impact of COVID-19-related lncRNAs on NSCLC remains unexplored.
View Article and Find Full Text PDFUnveiling the neuroprotective impact of virgin olive oil ingestion the microbiota-gut-brain axis.
Food Funct
January 2025
Department of Medical Biochemistry, Molecular Biology, and Immunology, School of Medicine, University of Seville, Av. Dr Fedriani s/n, 41009 Seville, Spain.
Article Synopsis
- The gut-brain axis is a two-way communication system between the gut and the brain, which significantly impacts overall health, particularly through dietary influences.
- Virgin olive oil (VOO) contains compounds like polyphenols and monounsaturated fatty acids that may enhance gut microbiota, promote beneficial bacteria, and support cognitive function by protecting neurons and regulating mood.
- While existing studies show positive effects of VOO on gut bacteria and brain health, they require improvement in terms of study design, standardization of VOO, and further exploration in human trials to validate findings and establish causality.
Integrating network pharmacology and animal experimental validation to investigate the mechanism of lotus leaf in obesity.
Int Immunopharmacol
January 2025
Heilongjiang Academy of Traditional Chinese Medicine, PR China. Electronic address:
Background: Lotus leaf and its extracts have been reported to exert various beneficial effects; however, their anti-obesity mechanisms remain relatively unclear. Therefore, we investigated the mechanism by which lotus leaf regulates obesity using network pharmacology, molecular docking, and animal experimentation.
Methods: Network pharmacology was used to identify potential targets and pathways through which lotus leaf regulates obesity.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!