Although antipsychotics are routinely used in the treatment of schizophrenia for the last decades, their precise mechanism of action is still unclear. In this study, we investigated changes in the PC12 cells' proteome under the influence of clozapine, risperidone, and haloperidol to identify protein pathways regulated by antipsychotics. Analysis of the protein profiles in two time points: after 12 and 24 h of incubation with drugs revealed significant alterations in 510 proteins. Further canonical pathway analysis revealed an inhibition of ciliary trophic factor signaling after treatment with haloperidol and showed a decrease in acute phase response signaling in the risperidone group. Interestingly, all tested drugs have caused changes in PC12 proteome which correspond to inhibition of cytokines: tumor necrosis factor (TNF) and transforming growth factor beta 1 (TGF-β1). We also found that the 12-h incubation with clozapine caused up-regulation of protein kinase A signaling and translation machinery. After 24 h of treatment with clozapine, the inhibition of the actin cytoskeleton signaling and Rho proteins signaling was revealed. The obtained results suggest that the mammalian target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) play a central role in the signal transduction of clozapine.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254727 | PMC |
| http://dx.doi.org/10.1007/s11064-021-03348-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Background: Prostaglandin E (PGE) in the rostral ventrolateral medulla (RVLM) has been recognized as a pivotal pressor substance in hypertension, yet understanding of its effects and origins in the RVLM remains largely elusive. This study aimed to elucidate the pivotal enzymes and molecular mechanisms underlying PGE synthesis induced by central Ang II (angiotensin II) and its implications in the heightened oxidative stress and sympathetic outflow in hypertension.
Methods And Results: RVLM microinjections of PGE and Tempol were administered in Wistar-Kyoto rats.
Ubiquitin specific peptidase 11 knockdown slows Huntington's disease progression via regulating mitochondrial dysfunction and neuronal damage depending on PTEN-mediated AKT pathway.
Mol Med
January 2025
Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China.
Background: Mitochondrial dysfunction and neuronal damage are major sign of cytopathology in Huntington's disease (HD), a neurodegenerative disease. Ubiquitin specific peptidase 11 (USP11) is a deubiquitinating enzyme involved in various physiological processes through regulating protein degradation. However, its specific role in HD is unclear.
View Article and Find Full Text PDFEffect of Hyaluronan Molecular Weight on the Stability and Biofunctionality of Microfibers Assembled by Interfacial Polyelectrolyte Complexation.
ACS Appl Mater Interfaces
January 2025
3B's Research Group, I3Bs─Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-694 Barco, Guimarães, Portugal.
Nervous system disorders are characterized by a progressive loss of function and structure of neurons that ultimately leads to a decline in cognitive and motor functions. In this study, we used interfacial polyelectrolyte complexation (IPC) to produce fibers for neural tissue regeneration. IPC is a processing method that allows spinning of sensitive biopolymers.
View Article and Find Full Text PDFPKR Inhibitor C16 Regulates HIV-gp120 Induced Neuronal Injury and Cognitive Impairment in Vivo and in Vitro Models.
Neurochem Res
January 2025
College of Pharmacy, Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, China.
To study the neuronal protective effect and its potential mechanism of C16 against gp120-induced cognitive impairment in vitro and in vivo. The NORT method was used to evaluate the short-term memory abilities of rats, the morphological changes in hippocampus were observed by Nissl staining. Cell viability and damage degree were detected by MTT and LDH.
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 PDFWant 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!