Delopment of a novel co-culture device of neuronal cells for construction of in vitro Alzheimer's disease model

Author(s):  
Takuma Maruyama ◽  
Seiichi Suzuki ◽  
Lui Yoshida ◽  
Kiyoshi Kotani ◽  
Yasuhiko Jimbo
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lishu Duan ◽  
Mufeng Hu ◽  
Joseph A. Tamm ◽  
Yelena Y. Grinberg ◽  
Fang Shen ◽  
...  

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.


2019 ◽  
Vol 08 (03) ◽  
pp. 27-38
Author(s):  
Julie Griffith ◽  
Shauna Northrup ◽  
Emma Cieslik ◽  
Marie Kelly-Worden

2019 ◽  
Vol 1718 ◽  
pp. 46-52 ◽  
Author(s):  
Minjie Tian ◽  
Xingjian Lin ◽  
Liang Wu ◽  
Jie Lu ◽  
Yingdong Zhang ◽  
...  

iScience ◽  
2020 ◽  
Vol 23 (12) ◽  
pp. 101823
Author(s):  
Catherine J. Yeates ◽  
Ankita Sarkar ◽  
Prajakta Deshpande ◽  
Madhuri Kango-Singh ◽  
Amit Singh

2021 ◽  
Author(s):  
Sarah Garder ◽  
Catharine Brady ◽  
Cameron Keeton ◽  
Anuj K Yadav ◽  
Sharath C Mallojjala ◽  
...  

<p>In the context of deep-tissue disease biomarker detection and analyte sensing of biologically relevant species, the impact of photoacoustic imaging has been profound. However, most photoacoustic imaging agents to date are based on the repurposing of existing fluorescent dye platforms that exhibit non-optimal properties for photoacoustic applications (e.g., high fluorescence quantum yield). Herein, we introduce two effective modifications to the hemicyanine dye to afford PA-HD, a new dye scaffold optimized for photoacoustic probe development. We observed a significant increase in the photoacoustic output, representing an increase in sensitivity of 4.8-fold and a red-shift of the λ<sub>abs</sub> from 690 nm to 745 nm to enable ratiometric imaging. Moreover, to demonstrate the generalizability and utility of our remodeling efforts, we developed three probes using common analyte-responsive triggers for beta-galactosidase activity (PA-HD-Gal), nitroreductase activity (PA-HD-NTR), and hydrogen peroxide (PA-HD-H<sub>2</sub>O<sub>2</sub>). The performance of each probe (responsiveness, selectivity) was evaluated <i>in vitro</i> and <i>in cellulo</i>. To showcase the enhance properties afforded by PA-HD for <i>in vivo</i> photoacoustic imaging, we employed an Alzheimer’s disease model to detect H<sub>2</sub>O<sub>2</sub>. In particular, the photoacoustic signal at 735 nm in the brains of 5xFAD mice (a murine model of Alzheimer’s disease) increased by 1.72 ± 0.20-fold relative to background indicating the presence of oxidative stress, whereas the change in wildtype mice was negligible (1.02 ± 0.14). These results were confirmed via ratiometric calibration which was not possible using the parent HD platform.</p>


Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1837 ◽  
Author(s):  
Uthaiwan Suttisansanee ◽  
Somsri Charoenkiatkul ◽  
Butsara Jongruaysup ◽  
Somying Tabtimsri ◽  
Dalad Siriwan ◽  
...  

Alzheimer’s disease (AD) is the most common form of dementia, characterized by chronic neuron loss and cognitive problems. Aggregated amyloid beta (Aβ) peptides, a product of cleaved amyloid precursor protein (APP) by beta-secretase 1 (BACE-1), have been indicated for the progressive pathogenesis of AD. Currently, screening for anti-AD compounds in foodstuffs is increasing, with promising results. Hence, the purpose of this study was to investigate the extraction conditions, phytochemical contents, and anti-AD properties, targeting Aβ peptides of Morus cf. nigra ‘Chiang Mai’ (MNCM) both in vitro and in vivo. Data showed that the aqueous extract of MNCM contained high amounts of cyanidin, keracyanin, and kuromanin as anthocyanidin and anthocyanins. The extract also strongly inhibited cholinesterases and BACE-1 in vitro. Moreover, MNCM extract prevented Aβ-induced neurotoxicity and promoted neurite outgrowth in neuronal cells. Interestingly, MNCM extract reduced Aβ1–42 peptides and improved locomotory coordination of Drosophila co-expressing human APP and BACE-1, specifically in the brain. These findings suggest that MNCM may be useful as an AD preventive agent by targeting Aβ formation.


2021 ◽  
Author(s):  
Fernanda Rodríguez-Enríquez ◽  
Dolores Viña ◽  
Eugenio Uriarte ◽  
José Ángel Fontenla ◽  
Maria João Matos

Abstract 3-(4’-Nitrobenzamido)coumarin (MJM255), a potent in vitro acetylcholinesterase (AChE) inhibitor, was selected as an in vivo candidate for the discovery of new therapeutic solutions for Alzheimer’s disease. Computational (in silico) studies showing the theoretical physicochemical properties indicate desirable a pharmacokinetic profile for this molecule to cross the blood-brain barrier (BBB). An in vivo study, using the object recognition test (ORT) mice model, was carried out. This compound exhibited a similar effect as eserine, a well-known AChE inhibitor able to cross the BBB.


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