FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2316120860> ?p ?o ?g. }

• W2316120860 endingPage "627" @default.
• W2316120860 startingPage "613" @default.
• W2316120860 abstract "Abstract Astrocytes are the predominant cell type in the nervous system and play a significant role in maintaining neuronal health and homeostasis. Recently, astrocyte dysfunction has been implicated in the pathogenesis of many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Astrocytes are thus an attractive new target for drug discovery for neurological disorders. Using astrocytes differentiated from human embryonic stem cells, we have developed an assay to identify compounds that protect against oxidative stress, a condition associated with many neurodegenerative diseases. This phenotypic oxidative stress assay has been optimized for high-throughput screening in a 1,536-well plate format. From a screen of approximately 4,100 bioactive tool compounds and approved drugs, we identified a set of 22 that acutely protect human astrocytes from the consequences of hydrogen peroxide-induced oxidative stress. Nine of these compounds were also found to be protective of induced pluripotent stem cell-differentiated astrocytes in a related assay. These compounds are thought to confer protection through hormesis, activating stress-response pathways and preconditioning astrocytes to handle subsequent exposure to hydrogen peroxide. In fact, four of these compounds were found to activate the antioxidant response element/nuclear factor-E2-related factor 2 pathway, a protective pathway induced by toxic insults. Our results demonstrate the relevancy and utility of using astrocytes differentiated from human stem cells as a disease model for drug discovery and development. Significance Astrocytes play a key role in neurological diseases. Drug discovery efforts that target astrocytes can identify novel therapeutics. Human astrocytes are difficult to obtain and thus are challenging to use for high-throughput screening, which requires large numbers of cells. Using human embryonic stem cell-derived astrocytes and an optimized astrocyte differentiation protocol, it was possible to screen approximately 4,100 compounds in titration to identify 22 that are cytoprotective of astrocytes. This study is the largest-scale high-throughput screen conducted using human astrocytes, with a total of 17,536 data points collected in the primary screen. The results demonstrate the relevancy and utility of using astrocytes differentiated from human stem cells as a disease model for drug discovery and development." @default.
• W2316120860 created "2016-06-24" @default.
• W2316120860 creator A5018433143 @default.
• W2316120860 creator A5021081868 @default.
• W2316120860 creator A5025240953 @default.
• W2316120860 creator A5035735276 @default.
• W2316120860 creator A5036261777 @default.
• W2316120860 creator A5038035464 @default.
• W2316120860 creator A5043714628 @default.
• W2316120860 creator A5044050021 @default.
• W2316120860 creator A5045144636 @default.
• W2316120860 creator A5059970716 @default.
• W2316120860 creator A5067514551 @default.
• W2316120860 date "2016-03-31" @default.
• W2316120860 modified "2023-10-14" @default.
• W2316120860 title "High-Throughput Phenotypic Screening of Human Astrocytes to Identify Compounds That Protect Against Oxidative Stress" @default.
• W2316120860 cites W1055875683 @default.
• W2316120860 cites W134928742 @default.
• W2316120860 cites W1523693806 @default.
• W2316120860 cites W1544419680 @default.
• W2316120860 cites W1572301294 @default.
• W2316120860 cites W1590514634 @default.
• W2316120860 cites W1824354915 @default.
• W2316120860 cites W1859730138 @default.
• W2316120860 cites W1963646113 @default.
• W2316120860 cites W1965566864 @default.
• W2316120860 cites W1968020616 @default.
• W2316120860 cites W1969925326 @default.
• W2316120860 cites W1970642506 @default.
• W2316120860 cites W1971125401 @default.
• W2316120860 cites W1973821691 @default.
• W2316120860 cites W1978366058 @default.
• W2316120860 cites W1981066521 @default.
• W2316120860 cites W1981128350 @default.
• W2316120860 cites W1984710087 @default.
• W2316120860 cites W1985031521 @default.
• W2316120860 cites W1986099314 @default.
• W2316120860 cites W1988570800 @default.
• W2316120860 cites W1989757536 @default.
• W2316120860 cites W1992022015 @default.
• W2316120860 cites W1994318934 @default.
• W2316120860 cites W1995959676 @default.
• W2316120860 cites W1998694879 @default.
• W2316120860 cites W2001553312 @default.
• W2316120860 cites W2005172933 @default.
• W2316120860 cites W2008634036 @default.
• W2316120860 cites W2008757142 @default.
• W2316120860 cites W2011342890 @default.
• W2316120860 cites W2012868552 @default.
• W2316120860 cites W2014078849 @default.
• W2316120860 cites W2015243552 @default.
• W2316120860 cites W2018382092 @default.
• W2316120860 cites W2021115145 @default.
• W2316120860 cites W2023327938 @default.
• W2316120860 cites W2027111347 @default.
• W2316120860 cites W2034879573 @default.
• W2316120860 cites W2036802953 @default.
• W2316120860 cites W2042066452 @default.
• W2316120860 cites W2045885471 @default.
• W2316120860 cites W2046543574 @default.
• W2316120860 cites W2049981080 @default.
• W2316120860 cites W2050382124 @default.
• W2316120860 cites W2050996473 @default.
• W2316120860 cites W2052853635 @default.
• W2316120860 cites W2058676566 @default.
• W2316120860 cites W2058834995 @default.
• W2316120860 cites W2060244901 @default.
• W2316120860 cites W2064004368 @default.
• W2316120860 cites W2067102002 @default.
• W2316120860 cites W2073752235 @default.
• W2316120860 cites W2077236166 @default.
• W2316120860 cites W2079645318 @default.
• W2316120860 cites W2081333442 @default.
• W2316120860 cites W2082245115 @default.
• W2316120860 cites W2083899916 @default.
• W2316120860 cites W2087296926 @default.
• W2316120860 cites W2089966673 @default.
• W2316120860 cites W2090306180 @default.
• W2316120860 cites W2091497743 @default.
• W2316120860 cites W2096000363 @default.
• W2316120860 cites W2098797526 @default.
• W2316120860 cites W2102563324 @default.
• W2316120860 cites W2103540774 @default.
• W2316120860 cites W2106531950 @default.
• W2316120860 cites W2107318881 @default.
• W2316120860 cites W2108236403 @default.
• W2316120860 cites W2108492672 @default.
• W2316120860 cites W2113887671 @default.
• W2316120860 cites W2117248404 @default.
• W2316120860 cites W2118661818 @default.
• W2316120860 cites W2122012141 @default.
• W2316120860 cites W2128879247 @default.
• W2316120860 cites W2129221272 @default.
• W2316120860 cites W2130419298 @default.
• W2316120860 cites W2132398264 @default.
• W2316120860 cites W2136921867 @default.
• W2316120860 cites W2137864613 @default.
• W2316120860 cites W2138271341 @default.

• next