Imidazoles as Serotonin Receptor Modulators for Treatment of Depression: Structural Insights and Structure–Activity Relationship Studies DOI Creative Commons
Kapil Kumar Goel, Somesh Thapliyal, Rajeev Kharb

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(9), P. 2208 - 2208

Published: Aug. 26, 2023

Serotoninergic signaling is identified as a crucial player in psychiatric disorders (notably depression), presenting it significant therapeutic target for treating such conditions. Inhibitors of serotoninergic (especially selective serotonin reuptake inhibitors (SSRI) or and norepinephrine (SNRI)) are prominently selected first-line therapy the treatment depression, which benefits via increasing low levels by blocking serotonin/norepinephrine thereby activity. While developing newer heterocyclic scaffolds to target/modulate serotonergic systems, imidazole-bearing pharmacophores have emerged. The imidazole-derived pharmacophore already demonstrated unique structural characteristics an electron-rich environment, ultimately resulting diverse range bioactivities. Therefore, current manuscript discloses specific modification activity relationship (SAR) attempted derivatization terms efficacy resultant inhibitor. We also featured landscape imidazole-based development, focusing on SAR studies against system depression. This study covers recent advancements synthetic methodologies imidazole derivatives development new molecules having antidepressant modulating along with their studies. focus provide insights into modulators

Language: Английский

Neuropathogenesis-on-chips for neurodegenerative diseases DOI Creative Commons
Sarnai Amartumur, Huong Mai Nguyen, Thuy Huynh

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 12, 2024

Abstract Developing diagnostics and treatments for neurodegenerative diseases (NDs) is challenging due to multifactorial pathogenesis that progresses gradually. Advanced in vitro systems recapitulate patient-like pathophysiology are emerging as alternatives conventional animal-based models. In this review, we explore the interconnected pathogenic features of different types ND, discuss general strategy modelling NDs using a microfluidic chip, introduce organoid-on-a-chip next advanced relevant model. Lastly, overview how these models being applied academic industrial drug development. The integration chips, stem cells, biotechnological devices promises provide valuable insights biomedical research developing diagnostic therapeutic solutions NDs.

Language: Английский

Citations

32
Neuromodulatory effect of vardenafil on aluminium chloride/d-galactose induced Alzheimer’s disease in rats: emphasis on amyloid-beta, p-tau, PI3K/Akt/p53 pathway, endoplasmic reticulum stress, and cellular senescence DOI Creative Commons
Heba H. Awad,

Mahmoud A. Desouky,

Alaa Zidan

et al.

Inflammopharmacology, Journal Year: 2023, Volume and Issue: 31(5), P. 2653 - 2673

Published: July 17, 2023

Abstract Dysregulation of protein homeostasis, proteostasis, is a distinctive hallmark many neurodegenerative disorders and aging. Deleteriously, the accumulation aberrant proteins in Alzheimer’s disease (AD) accompanied with marked collapse proteostasis network. The current study explored potential therapeutic effect vardenafil (VAR), phosphodiesterase-5 inhibitor, AlCl 3 / d -galactose ( -gal)-induced AD rats its possible underlying mechanisms. impact VAR treatment on neurobehavioral function, hippocampal tissue architecture, activity cholinergic system main enzymes were assessed utilizing at doses 0.3 mg/kg 1 mg/kg. Additionally, expression level amyloid-beta phosphorylated tau hippocampus figured out. Accordingly, higher dose was selected to contemplate Intriguingly, elevated cyclic guanosine monophosphate averted repressed proteasome by -gal; hence, might alleviate burden toxic aggregates AD. In addition, substantial reduction activating transcription factor 6-mediated endoplasmic reticulum stress demonstrated treatment. Notably, counteracted -gal-induced depletion nuclear erythroid 2-related 2 level. Moreover, anti-senescence via ability restore balance redox circuit. modulation phosphatidylinositol-3-kinase/protein kinase B/p53 pathway kappa B level, key regulator senescence-associated secretory phenotype mediators release, also elucidated. Altogether, these findings insinuate benefits management. Graphic abstract

Language: Английский

Citations

27
Evolving therapeutic interventions for the management and treatment of Alzheimer’s disease DOI
Faizan Ahmad, Anik Karan, Rashi Sharma

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 95, P. 102229 - 102229

Published: Feb. 15, 2024

Language: Английский

Citations

16
Types of memory, dementia, Alzheimer’s disease, and their various pathological cascades as targets for potential pharmacological drugs DOI
Ansab Akhtar, Siddharth Singh, Ravinder Kaushik

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102289 - 102289

Published: April 1, 2024

Language: Английский

Citations

14
Revolutionizing Alzheimer's treatment: Harnessing human serum albumin for targeted drug delivery and therapy advancements DOI

D. Shastri,

Vinit Raj,

Sang‐Kil Lee

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102379 - 102379

Published: June 18, 2024

Language: Английский

Citations

10
Butylated Hydroxytoluene (BHT) Protects SH-SY5Y Neuroblastoma Cells from Ferroptotic Cell Death: Insights from In Vitro and In Vivo Studies DOI Creative Commons

Parisa Faraji,

Astrid Borchert, Shahin Ahmadian

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 242 - 242

Published: Feb. 17, 2024

Ferroptosis is a special kind of programmed cell death that has been implicated in the pathogenesis large number human diseases. It involves dysregulated intracellular iron metabolism and uncontrolled lipid peroxidation, which together initiate ferroptotic signalling pathways leading to cellular suicide. Pharmacological interference with signal transduction may prevent death, thus patients suffering from ferroptosis-related diseases benefit such treatment. Butylated hydroxytoluene (BHT) an effective anti-oxidant frequently used oil chemistry cosmetics free-radical-mediated peroxidation. Since it functions as radical scavenger, previously reported interfere signalling. Here, we show BHT prevents RSL3- ML162-induced cultured neuroblastoma cells (SH-SY5Y) dose-dependent manner. RSL3-induced oxidation membrane lipids normalises inhibition catalytic activity glutathione peroxidase 4. The systemic application rat Alzheimer’s disease model prevented upregulation expression genes. Taken together, these data indicate interferes animal model.

Language: Английский

Citations

9
Alcohol Use Disorder and Dementia: A Review DOI Creative Commons

NM Zahr

Alcohol research, Journal Year: 2024, Volume and Issue: 44(1)

Published: Jan. 1, 2024

PURPOSE:By 2040, 21.6% of Americans will be over age 65, and the population those older than 85 is estimated to reach 14.4 million.Although not causative, a risk factor for dementia: every 5 years beyond doubles; approximately one-third are diagnosed with dementia.As current alcohol consumption among adults significantly higher compared previous generations, pressing question whether drinking increases Alzheimer's disease or other forms dementia.SEARCH METHODS: Databases explored included PubMed, Web Science, ScienceDirect.To accomplish this narrative review on effects dementia risk, literature covered clinical diagnoses, epidemiology, neuropsychology, postmortem pathology, neuroimaging biomarkers, translational studies.Searches conducted between January 12 August 1, 2023, following terms combinations: "aging," "alcoholism," "alcohol use disorder (AUD)," "brain," "CNS," "dementia," "Wernicke," "Korsakoff," "Alzheimer," "vascular," "frontotemporal," "Lewy body," "clinical," "diagnosis," "epidemiology," "pathology," "autopsy," "postmortem," "histology," "cognitive," "motor," "neuropsychological," "magnetic resonance," "imaging," "PET," "ligand," "degeneration," "atrophy," "translational," "rodent," "rat," "mouse," "model," "amyloid," "neurofibrillary tangles," "α-synuclein," "presenilin."When relevant, "species" (i.e., "humans" "other animals") was selected as an additional filter.Review articles were avoided when possible.SEARCH RESULTS: The two "alcoholism" "aging" retrieved about 1,350 papers; adding phrases-for example, "postmortem" resonance"-limited number fewer 100 papers.Using traditional term, "dementia" resulted in 876 citations, but using currently accepted term (AUD)" produced only 87 papers.Similarly, whereas "Alzheimer's" yielded 318 results, returned 40 citations.As pertinent pathology papers published 1950s recent animal models created early 2000s, referenced span 1957 2024.In total, more 5,000 considered; 400 herein referenced.DISCUSSION AND CONCLUSIONS: Chronic misuse accelerates brain aging contributes cognitive impairments, including mnemonic domain.The consensus studies from multiple disciplines, however, that can increase dementia, necessarily disease.Key issues consider include reversibility damage abstinence chronic degenerative progressive course disease, characteristic presence protein inclusions brains people which absent AUD.

Language: Английский

Citations

9
Microglial Responses to Alzheimer's Disease Pathology: Insights From “Omics” Studies DOI Open Access
Aquene N. Reid, Suman Jayadev, Katherine E. Prater

et al.

Glia, Journal Year: 2025, Volume and Issue: 73(3), P. 519 - 538

Published: Jan. 6, 2025

Human genetics studies lent firm evidence that microglia are key to Alzheimer's disease (AD) pathogenesis over a decade ago following the identification of AD-associated genes expressed in microglia-specific manner. However, while alterations microglial morphology and gene expression observed human postmortem brain tissue, mechanisms by which drive contribute AD pathology remain ill-defined. Numerous mouse models have been developed facilitate disambiguation biological underlying AD, incorporating amyloidosis, phosphorylated tau, or both. Over time, use multiple technologies including bulk tissue single cell transcriptomics, epigenomics, spatial proteomics, lipidomics, metabolomics shed light on heterogeneity phenotypes molecular patterns altered models. Each these 'omics provide unique information insight. Here, we review literature approaches findings methods synthesis knowledge generated applying AD.

Language: Английский

Citations

1
Investigating the neuroprotective effects of Dracocephalum moldavica extract and its effect on metabolomic profile of rat model of sporadic Alzheimer's disease DOI Creative Commons
Marjan Talebi, Seyed Abdulmajid Ayatollahi,

Mohammad Ali As’habi

et al.

Heliyon, Journal Year: 2025, Volume and Issue: 11(3), P. e42412 - e42412

Published: Feb. 1, 2025

Alzheimer's disease (AD) is a progressive condition marked by multiple underlying mechanisms. Therefore, the investigation of natural products that can target pathways presents potential gate for understanding and management AD. This study aimed to assess neuroprotective effects hydroalcoholic extract Dracocephalum moldavica (DM) on cognitive impairment, biomarker changes, putative metabolic in rat model AD induced intracerebroventricular streptozotocin (ICV-STZ). The DM was standardized quantified based examining total phenolic, flavonoid, rosmarinic acid, quercetin contents using colorimetry high-performance liquid chromatography (HPLC) methods. antioxidant evaluated 2,2-Diphenyl-1-picrylhydrazyl nitric oxide radical scavenging assays. Male Wistar rats were injected with STZ (3 mg/kg, single dose, bilateral ICV) induce sporadic (sAD) model. Following induction, orally administered (100, 200, 400 mg/kg/day) or donepezil (5 21 days. Cognitive function assessed radial arm water maze behavioral test. histopathological evaluations conducted cortex hippocampus regions. Matrix-assisted laser desorption/ionization-time flight mass spectrometry (MALDI-TOF MS) used metabolite changes various brain significantly attenuated dysfunction ICV-STZ according investigations. Thirty-two discriminating metabolites related amino acid metabolism; glutamate/gamma-aminobutyric acid/glutamine cycle; nucleotide lipid metabolism (glycerophospholipids, sphingomyelins, ceramides, phosphatidylserines, prostaglandins), glucose identified brains sAD simultaneously first time this Polyphenols may contribute regulation these pathways. After treatment extract, 10 from 32 ones altered tissue sAD, most commonly at doses 200 mg/kg. In conclusion, demonstrates upregulation/downregulation pathophysiological biomarkers such as adenine, glycerophosphoglycerol, inosine, prostaglandins, sphingomyelin sAD. These findings are consistent results outcomes.

Language: Английский

Citations

1
The Role of Hydrogen Sulfide (H2S) in Epigenetic Regulation of Neurodegenerative Diseases: A Systematic Review DOI Open Access

Bombonica Gabriela Dogaru,

Constantin Munteanu

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12555 - 12555

Published: Aug. 8, 2023

This review explores the emerging role of hydrogen sulfide (H

Language: Английский

Citations

23