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• W13770393 abstract "Amyotrophic lateral sclerosis (ALS) is the most common form of adult onset motor neuron disease and is characterized by the progressive degeneration and death of motor neurons. The pathologic mechanisms underlying ALS are poorly understood although our laboratory identified decreased levels of transthyretin (TTR), a protein that impacts the retinoid signaling pathway, in the cerebrospinal fluid of ALS patients. Differential expression of retinoid signaling components has been reported in ALS patients and transgenic animal models of familial ALS. We sought to further characterize TTR and retinoid signaling proteins in ALS and to evaluate the role of retinoid signaling in motor neuron cell death.Mass spectrometry and immunoblotting were used to investigate TTR. Immunohistochemistry using lumbar spinal cord tissue from ALS patients and non-neurologic disease controls was used to characterize retinoid signaling pathway proteins. Spinal cord tissue homogenates were used for co-immunoprecipitation studies and electrophoretic mobility shift assays. Motor neuron-enriched cultures established from embryonic day 14 rats were utilized for in vitro studies. RAR-mediated signaling was modulated with pan-agonists and isotype-specific agents and hydrogen peroxide used to model oxidative stress/injury.Altered post-translational modifications and high molecular weight species of the TTR protein were observed in ALS. Cellular retinoic acid binding protein-II (CRABP-II) and retinoic acid receptor beta (RARβ) exhibited increased nuclear localization in motor neurons of sporadic ALS patients. Protein-protein interactions (between CRABP-II and RARα or RARβ) did not differ although retinoic acid response element binding was increased in ALS as compared to controls. Treatment with a pan-RAR or RARβ-specific agonist significantly decreased oxidative stress-induced motor neuron cell death in vitro and genes downstream of RARβ were increased with treatment.Our results indicate that TTR genetic polymorphisms do not represent a novel susceptibility factor for ALS, although protein modification and aggregation appear to be altered in ALS. Localization of proteins of the retinoid signaling pathway is altered in ALS patients and these changes translate to the transcriptional level. Our in vitro work indicates that stimulating the RARs (particularly RARβ) is neuroprotective and that pharmacologic agents that target this nuclear receptor may be of value in slowing the progression of ALS." @default.
• W13770393 created "2016-06-24" @default.
• W13770393 creator A5014908119 @default.
• W13770393 date "2010-08-27" @default.
• W13770393 modified "2023-09-27" @default.
• W13770393 title "BEYOND BIOMARKER DISCOVERY: RETINOID SIGNALING IN MOTOR NEURONS AND AMYOTROPHIC LATERAL SCLEROSIS" @default.
• W13770393 cites W111663151 @default.
• W13770393 cites W1215506979 @default.
• W13770393 cites W1480786153 @default.
• W13770393 cites W1484397242 @default.
• W13770393 cites W1493169362 @default.
• W13770393 cites W1511517753 @default.
• W13770393 cites W1518030473 @default.
• W13770393 cites W1556861024 @default.
• W13770393 cites W1570165358 @default.
• W13770393 cites W1576678981 @default.
• W13770393 cites W1619082318 @default.
• W13770393 cites W167785202 @default.
• W13770393 cites W1823883969 @default.
• W13770393 cites W1894493322 @default.
• W13770393 cites W1915809219 @default.
• W13770393 cites W1940519961 @default.
• W13770393 cites W1950834793 @default.
• W13770393 cites W1963948469 @default.
• W13770393 cites W1964067973 @default.
• W13770393 cites W1964177214 @default.
• W13770393 cites W1965800022 @default.
• W13770393 cites W1966614683 @default.
• W13770393 cites W1967050619 @default.
• W13770393 cites W1967542752 @default.
• W13770393 cites W1968068652 @default.
• W13770393 cites W1968164494 @default.
• W13770393 cites W1969968664 @default.
• W13770393 cites W1970548725 @default.
• W13770393 cites W1971797190 @default.
• W13770393 cites W1972028705 @default.
• W13770393 cites W1973406416 @default.
• W13770393 cites W1973456315 @default.
• W13770393 cites W1974181990 @default.
• W13770393 cites W1975353932 @default.
• W13770393 cites W1975754280 @default.
• W13770393 cites W1977144473 @default.
• W13770393 cites W1977278297 @default.
• W13770393 cites W1978306592 @default.
• W13770393 cites W1978569326 @default.
• W13770393 cites W1978588293 @default.
• W13770393 cites W1978628739 @default.
• W13770393 cites W1978793403 @default.
• W13770393 cites W1981585359 @default.
• W13770393 cites W1982651451 @default.
• W13770393 cites W1983077552 @default.
• W13770393 cites W1983170848 @default.
• W13770393 cites W1983870655 @default.
• W13770393 cites W1984338458 @default.
• W13770393 cites W1984434170 @default.
• W13770393 cites W1984979116 @default.
• W13770393 cites W1985918137 @default.
• W13770393 cites W1986945403 @default.
• W13770393 cites W1987698430 @default.
• W13770393 cites W1987784344 @default.
• W13770393 cites W1988690555 @default.
• W13770393 cites W1990560195 @default.
• W13770393 cites W1991117617 @default.
• W13770393 cites W1991992962 @default.
• W13770393 cites W1992002234 @default.
• W13770393 cites W1992476369 @default.
• W13770393 cites W1992561071 @default.
• W13770393 cites W1993921528 @default.
• W13770393 cites W1994224789 @default.
• W13770393 cites W1994306276 @default.
• W13770393 cites W1994326152 @default.
• W13770393 cites W1994832401 @default.
• W13770393 cites W1995754186 @default.
• W13770393 cites W1996207491 @default.
• W13770393 cites W1997045117 @default.
• W13770393 cites W1997793569 @default.
• W13770393 cites W1997838784 @default.
• W13770393 cites W1998439486 @default.
• W13770393 cites W1998681801 @default.
• W13770393 cites W1998970893 @default.
• W13770393 cites W1999138692 @default.
• W13770393 cites W2001523160 @default.
• W13770393 cites W2001657042 @default.
• W13770393 cites W2003618511 @default.
• W13770393 cites W2003868797 @default.
• W13770393 cites W2004508412 @default.
• W13770393 cites W2005078338 @default.
• W13770393 cites W2005537737 @default.
• W13770393 cites W2005883936 @default.
• W13770393 cites W2007466152 @default.
• W13770393 cites W2008874237 @default.
• W13770393 cites W2009899606 @default.
• W13770393 cites W2010061595 @default.
• W13770393 cites W2010715880 @default.
• W13770393 cites W2012851706 @default.
• W13770393 cites W2013284164 @default.
• W13770393 cites W2013703514 @default.
• W13770393 cites W2013720811 @default.
• W13770393 cites W2014433622 @default.
• W13770393 cites W2015037203 @default.

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