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- W2896496883 abstract "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease selectively targeting motor neurons in the brain and spinal cord. The reasons for differential motor neuron susceptibility remain elusive. We developed a stem cell-based motor neuron assay to study cell-autonomous mechanisms causing motor neuron degeneration, with implications for ALS. A small-molecule screen identified cyclopiazonic acid (CPA) as a stressor to which stem cell-derived motor neurons were more sensitive than interneurons. CPA induced endoplasmic reticulum stress and the unfolded protein response. Furthermore, CPA resulted in an accelerated degeneration of motor neurons expressing human superoxide dismutase 1 (hSOD1) carrying the ALS-causing G93A mutation, compared to motor neurons expressing wild-type hSOD1. A secondary screen identified compounds that alleviated CPA-mediated motor neuron degeneration: three kinase inhibitors and tauroursodeoxycholic acid (TUDCA), a bile acid derivative. The neuroprotective effects of these compounds were validated in human stem cell-derived motor neurons carrying a mutated SOD1 allele (hSOD1A4V). Moreover, we found that the administration of TUDCA in an hSOD1G93A mouse model of ALS reduced muscle denervation. Jointly, these results provide insights into the mechanisms contributing to the preferential susceptibility of ALS motor neurons, and they demonstrate the utility of stem cell-derived motor neurons for the discovery of new neuroprotective compounds." @default.
- W2896496883 created "2018-10-26" @default.
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- W2896496883 date "2019-01-01" @default.
- W2896496883 modified "2023-10-06" @default.
- W2896496883 title "A Stem Cell-Based Screening Platform Identifies Compounds that Desensitize Motor Neurons to Endoplasmic Reticulum Stress" @default.
- W2896496883 cites W1967999689 @default.
- W2896496883 cites W1974540289 @default.
- W2896496883 cites W1975928461 @default.
- W2896496883 cites W1976276721 @default.
- W2896496883 cites W1977374662 @default.
- W2896496883 cites W1980053959 @default.
- W2896496883 cites W1983564332 @default.
- W2896496883 cites W1984332363 @default.
- W2896496883 cites W1988931872 @default.
- W2896496883 cites W1991815900 @default.
- W2896496883 cites W1993055783 @default.
- W2896496883 cites W1993064034 @default.
- W2896496883 cites W1995185770 @default.
- W2896496883 cites W1995686474 @default.
- W2896496883 cites W1996024251 @default.
- W2896496883 cites W1998626209 @default.
- W2896496883 cites W1999030622 @default.
- W2896496883 cites W1999319877 @default.
- W2896496883 cites W2000187136 @default.
- W2896496883 cites W2002134475 @default.
- W2896496883 cites W2005971787 @default.
- W2896496883 cites W2009066210 @default.
- W2896496883 cites W2009108898 @default.
- W2896496883 cites W2020437934 @default.
- W2896496883 cites W2023218749 @default.
- W2896496883 cites W2032063579 @default.
- W2896496883 cites W2033158384 @default.
- W2896496883 cites W2034424279 @default.
- W2896496883 cites W2034873294 @default.
- W2896496883 cites W2040628078 @default.
- W2896496883 cites W2040773899 @default.
- W2896496883 cites W2042251765 @default.
- W2896496883 cites W2042298557 @default.
- W2896496883 cites W2045960181 @default.
- W2896496883 cites W2048456744 @default.
- W2896496883 cites W2058183189 @default.
- W2896496883 cites W2059195318 @default.
- W2896496883 cites W2059355164 @default.
- W2896496883 cites W2060230550 @default.
- W2896496883 cites W2060900534 @default.
- W2896496883 cites W2061144812 @default.
- W2896496883 cites W2061173712 @default.
- W2896496883 cites W2063996210 @default.
- W2896496883 cites W2068669272 @default.
- W2896496883 cites W2073757903 @default.
- W2896496883 cites W2075511792 @default.
- W2896496883 cites W2077007919 @default.
- W2896496883 cites W2078338206 @default.
- W2896496883 cites W2079870118 @default.
- W2896496883 cites W2080901528 @default.
- W2896496883 cites W2093441343 @default.
- W2896496883 cites W2095699758 @default.
- W2896496883 cites W2099036911 @default.
- W2896496883 cites W2099976535 @default.
- W2896496883 cites W2101687573 @default.
- W2896496883 cites W2104135721 @default.
- W2896496883 cites W2107315373 @default.
- W2896496883 cites W2107660300 @default.
- W2896496883 cites W2107768418 @default.
- W2896496883 cites W2109679459 @default.
- W2896496883 cites W2114872355 @default.
- W2896496883 cites W2116110451 @default.
- W2896496883 cites W2131387907 @default.
- W2896496883 cites W2135107819 @default.
- W2896496883 cites W2140756516 @default.
- W2896496883 cites W2141453368 @default.
- W2896496883 cites W2143366726 @default.
- W2896496883 cites W2144508375 @default.
- W2896496883 cites W2144993965 @default.
- W2896496883 cites W2146546145 @default.
- W2896496883 cites W2147802916 @default.
- W2896496883 cites W2149927906 @default.
- W2896496883 cites W2153074213 @default.
- W2896496883 cites W2154923417 @default.
- W2896496883 cites W2157076525 @default.
- W2896496883 cites W2157404312 @default.
- W2896496883 cites W2160059242 @default.