CRISPR/Cas-Based Approaches to Study Schizophrenia and Other Neurodevelopmental Disorders DOI Open Access
Artemii O. Kurishev, Dmitry S. Karpov, Nonna I. Nadolinskaia

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 24(1), P. 241 - 241

Published: Dec. 23, 2022

The study of diseases the central nervous system (CNS) at molecular level is challenging because complexity neural circuits and huge number specialized cell types. Moreover, genomic association studies have revealed complex genetic architecture schizophrenia other genetically determined mental disorders. Investigating such to decipher basis CNS pathologies requires use high-throughput models as cells their derivatives. time coming for technologies based on CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat)/Cas systems manipulate multiple targets. CRISPR/Cas provide desired complexity, versatility, flexibility create novel tools capable both altering DNA sequence affecting its function higher levels information flow. make it possible find investigate intricate relationship between genotype phenotype neuronal cells. purpose this review discuss innovative CRISPR-based approaches studying mechanisms using cellular models.

Language: Английский

Advanced 3D Models of Human Brain Tissue Using Neural Cell Lines: State-of-the-Art and Future Prospects DOI Creative Commons
Rachele Fabbri, Ludovica Cacopardo, Arti Ahluwalia

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(8), P. 1181 - 1181

Published: April 18, 2023

Human-relevant three-dimensional (3D) models of cerebral tissue can be invaluable tools to boost our understanding the cellular mechanisms underlying brain pathophysiology. Nowadays, accessibility, isolation and harvesting human neural cells represents a bottleneck for obtaining reproducible accurate gaining insights in fields oncology, neurodegenerative diseases toxicology. In this scenario, given their low cost, ease culture reproducibility, cell lines constitute key tool developing usable reliable brain. Here, we review most recent advances 3D constructs laden with lines, highlighting advantages limitations possible future applications.

Language: Английский

Citations

21
Design, synthesis and bioevaluation of 1,2,4-thiadiazolidine-3,5-dione derivatives as potential GSK-3β inhibitors for the treatment of Alzheimer's disease DOI

Yongxi Dong,

Jun Lü, Shanhui Zhang

et al.

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 134, P. 106446 - 106446

Published: Feb. 25, 2023

Language: Английский

Citations

17
Implantation of MSC Spheroid-derived 3D Decellularized ECM Enriched with the MSC Secretome Ameliorates Traumatic Brain Injury and Promotes Brain Repair DOI
Grace H Chen,

Kee‐Chin Sia,

Shaowen Liu

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 315, P. 122941 - 122941

Published: Nov. 1, 2024

Language: Английский

Citations

4
Toward the Treatment of Glioblastoma Tumors Using Photoactivated Chemotherapy: In Vitro Evaluation of Efficacy and Safety DOI Creative Commons
Sina Katharina Goetzfried, Matthijs L. A. Hakkennes, Anja Busemann

et al.

ACS Pharmacology & Translational Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Glioblastoma multiforme (GBM) is highly aggressive, necessitating new therapies. Photoactivated chemotherapy (PACT) offers a promising approach by activating prodrugs with visible light at the tumor site. This study evaluated anticancer activity of ruthenium-based PACT compounds in U-87MG glioblastoma cells and their safety SH-SY5Y neuron-like cells. The compound [3](PF6)2 showed light-activated effects cells, while [1](PF6)2 was inactive, [2](PF6)2 nonactivated. Interestingly, increased cell proliferation, similar to donepezil, without causing death. Increased Ca2+ uptake observed, possibly via interaction AMPA receptor, as suggested docking studies. These findings suggest may serve potential treatments for GBM, effectively attacking cancer preserving healthy neuronal

Language: Английский

Citations

0
Corticosteroid‐regulated gene transcription in SH‐SY5Y‐derived neurons: Insights into the mineralocorticoid and glucocorticoid receptor‐mediated response DOI Open Access

Justina F. Lugenbühl,

Clara Snijders,

Cameron D. Pernia

et al.

Journal of Neuroendocrinology, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Abstract Post‐traumatic stress disorder (PTSD) and major depressive (MDD) are debilitating stress‐related psychiatric disorders that can develop following exposure to traumatic events or chronic in some individuals. The neurobiological processes leading disease remain largely unknown. Among others, these characterized by a dysregulated hypothalamic–pituitary–adrenal axis, which is regulated the glucocorticoid receptor (GR) mineralocorticoid (MR). This leads altered downstream corticosteroid‐induced gene expression. In vitro models promising tools investigate specific underpinnings of response brain. Here, we investigated suitability SH‐SY5Y‐derived neurons as cost‐efficient system study role GR MR neuronal response. were characterized, exposed corticosteroids, analyzed on transcriptomic proteomic levels. We show (i) express sufficient seemingly functional allow transcription, (ii) three corticosteroids cortisol, dexamethasone, aldosterone, induced similar effects, (iii) antagonist spironolactone mildly attenuated effects dexamethasone FKBP5 , DUSP1 SUPV3L1 . Mifepristone did not significantly alter effect aldosterone. (iv) Integrating alterations corticosteroid‐exposed with those iPSC‐derived showed concordant two systems. To determine translational validity, compared expression transcriptome postmortem brain samples from individuals PTSD MDD, yielding stronger negative correlations corticosteroid signatures than MDD signatures. Upon further refinement validation, may serve simplistic tool implicated molecular networks around MR. Strengthening our insight into receptors' functions improves understanding commonly such MDD.

Language: Английский

Citations

0
The Role and Importance of Neuroinflammation in Biopsychiatry DOI Creative Commons
Hayriye Soytürk,

Ümit Kılıç,

Cansu Önal

et al.

IntechOpen eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Neuroinflammation is an inflammatory response that affects the central nervous system. This process involves activation of immune cells like microglia and astrocytes, as well production chemicals cytokines chemokines. can be caused by a variety circumstances, including trauma, infection, autoimmune illnesses, environmental factors, any stress scenario, neurodegenerative diseases. thought to connected with psychiatric disorders. These illnesses include depression, anxiety disorders, schizophrenia, bipolar disorder. Research in biological neuropsychiatry assist establishing future treatment options demonstrating how neuroinflammation contributes illness. book chapter explains major contributor mental this topic significant study therapy.

Language: Английский

Citations

0
NMR Metabolomic Profiling of Differentiated SH-SY5Y Neuronal Cells: Amyloid-β Toxicity and Protective Effects of Galantamine and Lycorine DOI Creative Commons
Arian Kola, Filippo Costanti, Jordan Kahfi

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 525 - 525

Published: April 1, 2025

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by metabolic dysregulation, oxidative stress, amyloid-β (Aβ) aggregation, metal dyshomeostasis, and mitochondrial dysfunction. Current treatments provide only symptomatic relief, highlighting the need for novel therapeutic strategies. This study investigates effects of alkaloids galantamine (GAL) lycorine (LYC) in differentiated SH-SY5Y neuroblastoma cells, an established vitro model AD, which acquire neuronal phenotype upon differentiation. Using untargeted targeted NMR-based metabolomics combined with multivariate statistical analysis, we analyzed extracellular profiles under basal conditions following Aβ42 exposure, both presence absence GAL LYC. Our findings reveal distinct responses to Aβ toxicity, significant alterations pyruvate glutamine metabolism. Both LYC contributed restoration lysine homeostasis, but had more pronounced effect, better sustaining cellular energy balance function. Unlike LYC, treatment was associated accumulation, response between two compounds. These variations may reflect mechanisms action, potentially influencing their roles counteracting Aβ-induced toxicity. highlights value profiling assessing neuroprotective agents reinforces potential natural this context.

Language: Английский

Citations

0
Bexarotene Promotes Neuroblastoma SH-SY5Y Cell Differentiation to Mature Neurons with Decreased Proliferation DOI
Fan Zhang, Kai Gao,

Junjiao Zhang

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Language: Английский

Citations

0
Mitochondria transfer as a potential therapeutic mechanism in Alzheimer’s disease-like pathology DOI

Mohil Mishra,

Shalini Raik, Vidya Rattan

et al.

Brain Research, Journal Year: 2023, Volume and Issue: 1819, P. 148544 - 148544

Published: Aug. 22, 2023

Language: Английский

Citations

9
Epidermal Neural Crest Stem Cell Conditioned Medium Enhances Spinal Cord Injury Recovery via PI3K/AKT-Mediated Neuronal Apoptosis Suppression DOI Creative Commons
Ziqian Ma, Tao Liu, Liang Liu

et al.

Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(10), P. 2854 - 2870

Published: July 18, 2024

Abstract This study aimed to assess the impact of conditioned medium from epidermal neural crest stem cells (EPI-NCSCs-CM) on functional recovery following spinal cord injury (SCI), while also exploring involvement PI3K-AKT signaling pathway in regulating neuronal apoptosis. EPI-NCSCs were isolated 10-day-old Sprague-Dawley rats and cultured for 48 h obtain EPI-NCSC-CM. SHSY-5Y subjected with H 2 O treatment induce Cell viability survival rates evaluated using CCK-8 assay calcein-AM/PI staining. SCI contusion model was established adult recovery, utilizing Basso, Beattie Bresnahan (BBB) scoring system, inclined test, footprint observation. Neurological restoration after analyzed through electrophysiological recordings. Histological analysis included hematoxylin eosin (H&E) staining Nissl evaluate tissue organization. Apoptosis oxidative stress levels assessed TUNEL ROS detection methods. Additionally, western blotting performed examine expression apoptotic markers proteins related PI3K/AKT pathway. EPI-NCSC-CM significantly facilitated histological by inhibiting apoptosis modulation Administration EPI-NCSCs-CM alleviated H2O2-induced neurotoxicity vitro. The use LY294002, a PI3K inhibitor, underscored crucial role contributes ongoing exploration molecular pathways involved (SCI) repair, focusing therapeutic potential research findings indicate that exerts neuroprotective effect suppressing activation rats. These results highlight promising as strategy SCI, emphasizing significance mediating its beneficial effects. Graphical

Language: Английский

Citations

3