In vitro neuroprotective effects of farnesene sesquiterpene on alzheimer’s disease model of differentiated neuroblastoma cell line

2020 ◽  
pp. 1-10 ◽  
Author(s):  
Mehmet Enes Arslan ◽  
Hasan Türkez ◽  
Adil Mardinoğlu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Line ◽  
Neuroblastoma Cell ◽  
Disease Model ◽  
Neuroblastoma Cell Line ◽  
Neuroprotective Effects

scholarly journals Camptothecin Regulates Microglia Polarization and Exerts Neuroprotective Effects via Activating AKT/Nrf2/HO-1 and Inhibiting NF-κB Pathways In Vivo and In Vitro

2021 ◽  
Vol 12 ◽  
Author(s):  
Dewei He ◽  
Shoupeng Fu ◽  
Ang Zhou ◽  
Yingchun Su ◽  
Xiyu Gao ◽  
...  
Keyword(s):  
Cell Line ◽  
Inflammatory Responses ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Line ◽  
Mechanism Study ◽  
Antitumor Effects ◽  
Neuroprotective Effects ◽  
Microglia Polarization

Microglia, the main immune cells in the brain, participate in the innate immune response in the central nervous system (CNS). Studies have shown that microglia can be polarized into pro-inflammatory M1 and anti-inflammatory M2 phenotypes. Accumulated evidence suggests that over-activated M1 microglia release pro-inflammatory mediators that damage neurons and lead to Parkinson’s disease (PD). In contrast, M2 microglia release neuroprotective factors and exert the effects of neuroprotection. Camptothecin (CPT), an extract of the plant Camptotheca acuminate, has been reported to have anti-inflammation and antitumor effects. However, the effect of CPT on microglia polarization and microglia-mediated inflammation responses has not been reported. In our study we found that CPT improved motor performance of mice and reduced the loss of neurons in the substantia nigra (SN) of the midbrain in LPS-injected mice. In the mechanism study, we found that CPT inhibited M1 polarization of microglia and promotes M2 polarization via the AKT/Nrf2/HO-1 and NF-κB signals. Furthermore, CPT protected the neuroblastoma cell line SH-SY5Y and dopaminergic neuron cell line MN9D from damage mediated by microglia activation. In conclusion, our results demonstrate that CPT regulates the microglia polarization phenotype via activating AKT/Nrf2/HO-1 and inhibiting NF-κB pathways, inhibits neuro-inflammatory responses, and exerts neuroprotective effects in vivo and in vitro.

Angiotensin II triggers autophagy and apoptosis in PC12 cell line: An in vitro Alzheimer’s disease model

2019 ◽  
Vol 1718 ◽  
pp. 46-52 ◽  
Author(s):  
Minjie Tian ◽  
Xingjian Lin ◽  
Liang Wu ◽  
Jie Lu ◽  
Yingdong Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Angiotensin Ii ◽  
Cell Line ◽  
Pc12 Cell ◽  
Disease Model ◽  
Pc12 Cell Line

scholarly journals Histidyl-Proline Diketopiperazine Isomers as Multipotent Anti-Alzheimer Drug Candidates

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 737 ◽  
Author(s):  
Hasan Turkez ◽  
Ivana Cacciatore ◽  
Mehmet Enes Arslan ◽  
Erika Fornasari ◽  
Lisa Marinelli ◽  
...  
Keyword(s):  
Cell Line ◽  
Human Lymphocytes ◽  
Neuroblastoma Cell ◽  
Disease Model ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma Cell ◽  
Gene Expressions ◽  
Damage Potential ◽  
Human Neuroblastoma

Cyclic dipeptides administered by both parenteral and oral routes are suggested as promising candidates for the treatment of neurodegeneration-related pathologies. In this study, we tested Cyclo (His-Pro) isomers (cHP1-4) for their anti-Alzheimer potential using a differentiated human neuroblastoma cell line (SH-SY5Y) as an Alzheimer’s disease (AD) experimental model. The SH-SY5Y cell line was differentiated by the application of all-trans retinoic acid (RA) to obtain mature neuron-like cells. Amyloid-beta 1-42 (Aβ1-42) peptides, the main effector in AD, were administered to the differentiated cell cultures to constitute the in vitro disease model. Next, we performed cell viability analyses 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays) to investigate the neuroprotective concentrations of cyclodipeptides using the in vitro AD model. We evaluated acetylcholinesterase (AChE), α- and β-secretase activities (TACE and BACE1), antioxidant potency, and apoptotic/necrotic properties and performed global gene expression analysis to understand the main mechanism behind the neuroprotective features of cHP1-4. Moreover, we conducted sister chromatid exchange (SCE), micronucleus (MN), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) analyses to evaluate the genotoxic damage potential after applications with cHP1-4 on cultured human lymphocytes. Our results revealed that cHP1-4 isomers provide a different degree of neuroprotection against Aβ1-42-induced cell death on the in vitro AD model. The applications with cHP1-4 isomers altered the activity of AChE but not the activity of TACE and BACE1. Our analysis indicated that the cHP1-4 increased the total antioxidant capacity without altering total oxidative status levels in the cellular AD model and that cHP1-4 modulated the alterations of gene expressions by Aβ1-42 exposure. We also observed that cHP1-4 exhibited noncytotoxic and non-genotoxic features in cultured human whole blood cells. In conclusion, cHP1-4 isomers, especially cHP4, have been explored as novel promising therapeutics against AD.

Neuroprotective effects of PrxI over-expression in an in vitro human Alzheimer's disease model

2013 ◽  
Vol 114 (3) ◽  
pp. 708-715 ◽  
Author(s):  
Annamaria Cimini ◽  
Roberta Gentile ◽  
Francesco Angelucci ◽  
Elisabetta Benedetti ◽  
Giuseppina Pitari ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Model ◽  
Neuroprotective Effects ◽  
Over Expression

scholarly journals Arrayed CRISPR reveals genetic regulators of tau aggregation, autophagy and mitochondria in Alzheimer’s disease model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lishu Duan ◽  
Mufeng Hu ◽  
Joseph A. Tamm ◽  
Yelena Y. Grinberg ◽  
Fang Shen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Discovery ◽  
Disease Model ◽  
Mitochondrial Morphology ◽  
Individual Gene ◽  
Human Genes ◽  
Future Drug ◽  
Tau Aggregation

AbstractAlzheimer’s disease (AD) is a common neurodegenerative disease with poor prognosis. New options for drug discovery targets are needed. We developed an imaging based arrayed CRISPR method to interrogate the human genome for modulation of in vitro correlates of AD features, and used this to assess 1525 human genes related to tau aggregation, autophagy and mitochondria. This work revealed (I) a network of tau aggregation modulators including the NF-κB pathway and inflammatory signaling, (II) a correlation between mitochondrial morphology, respiratory function and transcriptomics, (III) machine learning predicted novel roles of genes and pathways in autophagic processes and (IV) individual gene function inferences and interactions among biological processes via multi-feature clustering. These studies provide a platform to interrogate underexplored aspects of AD biology and offer several specific hypotheses for future drug discovery efforts.

scholarly journals Synergistic Action of Flavonoids, Baicalein, and Daidzein in Estrogenic and Neuroprotective Effects: A Development of Potential Health Products and Therapeutic Drugs against Alzheimer’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Roy C. Y. Choi ◽  
Judy T. T. Zhu ◽  
Amanda W. Y. Yung ◽  
Pinky S. C. Lee ◽  
Sherry L. Xu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transcriptional Activation ◽  
Estrogenic Activity ◽  
Neuroprotective Effects ◽  
Potential Health ◽  
Amyloid A ◽  
Therapeutic Drugs ◽  
Health Products

Despite the classical hormonal effect, estrogen has been reported to mediate neuroprotection in the brain, which leads to the searching of estrogen-like substances for treating neurodegenerative diseases. Flavonoids, a group of natural compounds, are well known to possess estrogenic effects and used to substitute estrogen, that is, phytoestrogen. Flavonoid serves as one of the potential targets for the development of natural supplements and therapeutic drugs against different diseases. The neuroprotection activity of flavonoids was chosen for a possible development of anti-Alzheimer's drugs or food supplements. The estrogenic activity of two flavonoids, baicalein and daidzein, were demonstrated by their strong abilities in stimulating estrogen receptor phosphorylation and transcriptional activation of estrogen responsive element in MCF-7 breast cells. The neuroprotection effects of flavonoids againstβ-amyloid (Aβ) were revealed by their inhibition effects onin vitroAβaggregation and Aβ-induced cytotoxicity in PC12 neuronal cells. More importantly, the estrogenic and neuroprotective activities of individual flavonoid could be further enhanced by the cotreatment in the cultures. Taken together, this synergistic effect of baicalein and daidzein might serve as a method to improve the therapeutic efficacy of different flavonoids against Aβ, which might be crucial in developing those flavonoidsin treating Alzheimer's disease in the future.

scholarly journals Hypoglycemia, Hyperglycemia and Astaxanthin: An <i>in Vitro</i> Alzheimer’s Disease Model

2019 ◽  
Vol 08 (03) ◽  
pp. 27-38
Author(s):  
Julie Griffith ◽  
Shauna Northrup ◽  
Emma Cieslik ◽  
Marie Kelly-Worden
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Model

scholarly journals A novel in vitro assay model developed to measure both extracellular and intracellular acetylcholine levels for screening cholinergic agents

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258420
Author(s):  
Ryohei Tanaka-Kanegae ◽  
Koichiro Hamada
Keyword(s):  
Cell Line ◽  
Neuroblastoma Cell ◽  
Cholinergic Neurons ◽  
Mechanisms Of Action ◽  
Neuroblastoma Cell Line ◽  
Ache Inhibitor ◽  
Vitro Assay ◽  
Food Ingredients ◽  
High Doses

Background Cholinergic neurons utilize choline (Ch) to synthetize acetylcholine (ACh) and contain a high-affinity Ch transporter, Ch acetyltransferase (ChAT), ACh receptors, and acetylcholinesterase (AChE). As the depletion or malfunction of each component of the cholinergic system has been reported in patients with dementia, many studies have sought to evaluate whether treatment candidates affect each of the cholinergic components. The associated changes in the cholinergic components may be reflected by intra- or extra-cellular ACh levels, with an increase in extracellular ACh levels occurring following AChE inhibition. We hypothesized that increases in intracellular ACh levels can be more sensitively detected than those in extracellular ACh levels, thereby capturing subtle effects in the cholinergic components other than AChE. The objective of this study was to test this hypothesis. Methods We developed an in vitro model to measure both extracellular and intracellular ACh levels using the human cholinergic neuroblastoma cell line, LA-N-2, which have been reported to express Ch transporter, ChAT, muscarinic ACh receptor (mAChR), and AChE. With this model, we evaluated several drug compounds and food constituents reported to improve cholinergic function through various mechanisms. In addition, we conducted western blotting to identify the subtype of mAChR that is expressed on the cell line. Results Our cell-based assay system was capable of detecting increases in extracellular ACh levels induced by an AChE inhibitor at relatively high doses, as well as increases in intracellular ACh levels following the administration of lower AChE-inhibitor doses and an mAChR agonist. Moreover, increases in intracellular ACh levels were observed even after treatment with food constituents that have different mechanisms of action, such as Ch provision and ChAT activation. In addition, we revealed that LA-N-2 cells expressed mAChR M2. Conclusion The findings support our hypothesis and indicate that the developed assay model can broadly screen compounds from drugs to food ingredients, with varying strengths and mechanisms of action, to develop treatments for ACh-relevant phenomena, including dementia and aging-related cognitive decline.

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