Neuropathogenesis-on-chips for neurodegenerative diseases

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 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.

Язык: Английский

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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

Inflammopharmacology, Год журнала: 2023, Номер 31(5), С. 2653 - 2673

Опубликована: Июль 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

Язык: Английский

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Evolving therapeutic interventions for the management and treatment of Alzheimer’s disease

Ageing Research Reviews, Год журнала: 2024, Номер 95, С. 102229 - 102229

Опубликована: Фев. 15, 2024

Язык: Английский

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Types of memory, dementia, Alzheimer’s disease, and their various pathological cascades as targets for potential pharmacological drugs

Ageing Research Reviews, Год журнала: 2024, Номер 96, С. 102289 - 102289

Опубликована: Апрель 1, 2024

Язык: Английский

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

Ageing Research Reviews, Год журнала: 2024, Номер 99, С. 102379 - 102379

Опубликована: Июнь 18, 2024

Язык: Английский

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

Antioxidants, Год журнала: 2024, Номер 13(2), С. 242 - 242

Опубликована: Фев. 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.

Язык: Английский

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Alcohol Use Disorder and Dementia: A Review

Alcohol research, Год журнала: 2024, Номер 44(1)

Опубликована: Янв. 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.

Язык: Английский

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Microglial Responses to Alzheimer's Disease Pathology: Insights From “Omics” Studies

Glia, Год журнала: 2025, Номер 73(3), С. 519 - 538

Опубликована: Янв. 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.

Язык: Английский

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

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(16), С. 12555 - 12555

Опубликована: Авг. 8, 2023

This review explores the emerging role of hydrogen sulfide (H

Язык: Английский

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Insight into the emerging and common experimental in-vivo models of Alzheimer’s disease

Laboratory Animal Research, Год журнала: 2023, Номер 39(1)

Опубликована: Дек. 11, 2023

Abstract Alzheimer’s disease (AD) is a multifactorial, rapidly progressing neurodegenerative disorder. As the exact cause of still unclear, drug development very challenging. This review encompasses commonly used AD models involving various chemicals, heavy metals and endogenous substances induced transgenic models. It also provides insight into reliable emerging that may overcome shortcomings associated with available Chemicals like streptozotocin, scopolamine, colchicine okadaic acid render animal susceptible to neuroinflammation oxidative stress neurodegeneration along amyloid-β deposition tau hyperphosphorylation. Similarly, acrolein 1–42 are efficient in inducing major pathologies AD. Heavy aluminum fluoride mixture these have been reported induce neurotoxicity therefore as for Transgenic developed result knock-in or knock-out certain genes including PDAPP, APP23, Tg2576, APP/PS1, 3 × Tg 5 FAD incorporated this study. Further, advanced pathomimetic provided particular interest here which will add on current knowledge aid process deepen our understanding related pathogenesis. These newly discovered include oAβ25-35 model, model expressing 82-kDa ChAT, oDGal mouse APP rat. study selection suitable novel potent therapeutics exploring detailed pathogenic mechanism Graphical abstract

Язык: Английский

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