Matches in SemOpenAlex for { <https://semopenalex.org/work/W2140661454> ?p ?o ?g. }
- W2140661454 endingPage "2022" @default.
- W2140661454 startingPage "2005" @default.
- W2140661454 abstract "Neuronal ceroid lipofuscinosis (NCL) comprises ∼13 genetically distinct lysosomal disorders primarily affecting the central nervous system. Here we report successful reprograming of patient fibroblasts into induced pluripotent stem cells (iPSCs) for the two most common NCL subtypes: classic late-infantile NCL, caused by TPP1(CLN2) mutation, and juvenile NCL, caused by CLN3 mutation. CLN2/TPP1- and CLN3-iPSCs displayed overlapping but distinct biochemical and morphological abnormalities within the endosomal-lysosomal system. In neuronal derivatives, further abnormalities were observed in mitochondria, Golgi and endoplasmic reticulum. While lysosomal storage was undetectable in iPSCs, progressive disease subtype-specific storage material was evident upon neural differentiation and was rescued by reintroducing the non-mutated NCL proteins. In proof-of-concept studies, we further documented differential effects of potential small molecule TPP1 activity inducers. Fenofibrate and gemfibrozil, previously reported to induce TPP1 activity in control cells, failed to increase TPP1 activity in patient iPSC-derived neural progenitor cells. Conversely, nonsense suppression by PTC124 resulted in both an increase of TPP1 activity and attenuation of neuropathology in patient iPSC-derived neural progenitor cells. This study therefore documents the high value of this powerful new set of tools for improved drug screening and for investigating early mechanisms driving NCL pathogenesis." @default.
- W2140661454 created "2016-06-24" @default.
- W2140661454 creator A5005997788 @default.
- W2140661454 creator A5011464526 @default.
- W2140661454 creator A5017311050 @default.
- W2140661454 creator A5022629938 @default.
- W2140661454 creator A5023209543 @default.
- W2140661454 creator A5024139961 @default.
- W2140661454 creator A5024787167 @default.
- W2140661454 creator A5029615614 @default.
- W2140661454 creator A5034338983 @default.
- W2140661454 creator A5039229902 @default.
- W2140661454 creator A5044329623 @default.
- W2140661454 creator A5049497575 @default.
- W2140661454 creator A5059133881 @default.
- W2140661454 creator A5060882865 @default.
- W2140661454 creator A5064433832 @default.
- W2140661454 creator A5064569338 @default.
- W2140661454 creator A5069049128 @default.
- W2140661454 creator A5075726671 @default.
- W2140661454 creator A5078962332 @default.
- W2140661454 creator A5081229010 @default.
- W2140661454 creator A5081645261 @default.
- W2140661454 creator A5081861600 @default.
- W2140661454 creator A5082252371 @default.
- W2140661454 date "2013-11-23" @default.
- W2140661454 modified "2023-09-30" @default.
- W2140661454 title "Human iPSC models of neuronal ceroid lipofuscinosis capture distinct effects of TPP1 and CLN3 mutations on the endocytic pathway" @default.
- W2140661454 cites W1503369988 @default.
- W2140661454 cites W1529584506 @default.
- W2140661454 cites W1550967330 @default.
- W2140661454 cites W1964040548 @default.
- W2140661454 cites W1966504370 @default.
- W2140661454 cites W1972612511 @default.
- W2140661454 cites W1973572007 @default.
- W2140661454 cites W1975545686 @default.
- W2140661454 cites W1975614370 @default.
- W2140661454 cites W1976093612 @default.
- W2140661454 cites W1979182028 @default.
- W2140661454 cites W1979216037 @default.
- W2140661454 cites W1986233321 @default.
- W2140661454 cites W1988099826 @default.
- W2140661454 cites W1992795339 @default.
- W2140661454 cites W1999371762 @default.
- W2140661454 cites W2002179012 @default.
- W2140661454 cites W2005144914 @default.
- W2140661454 cites W2012530297 @default.
- W2140661454 cites W2013005253 @default.
- W2140661454 cites W2014641941 @default.
- W2140661454 cites W2025739015 @default.
- W2140661454 cites W2027330624 @default.
- W2140661454 cites W2037228773 @default.
- W2140661454 cites W2039756269 @default.
- W2140661454 cites W2043638634 @default.
- W2140661454 cites W2044731711 @default.
- W2140661454 cites W2048834720 @default.
- W2140661454 cites W2049983395 @default.
- W2140661454 cites W2051689456 @default.
- W2140661454 cites W2060441085 @default.
- W2140661454 cites W2078078890 @default.
- W2140661454 cites W2081200794 @default.
- W2140661454 cites W2081925752 @default.
- W2140661454 cites W2085811948 @default.
- W2140661454 cites W2095965043 @default.
- W2140661454 cites W2100959085 @default.
- W2140661454 cites W2107554012 @default.
- W2140661454 cites W2111964251 @default.
- W2140661454 cites W2112620963 @default.
- W2140661454 cites W2115679330 @default.
- W2140661454 cites W2115991151 @default.
- W2140661454 cites W2121941288 @default.
- W2140661454 cites W2125987139 @default.
- W2140661454 cites W2126213759 @default.
- W2140661454 cites W2127088485 @default.
- W2140661454 cites W2135463801 @default.
- W2140661454 cites W2141010238 @default.
- W2140661454 cites W2142623488 @default.
- W2140661454 cites W2148374260 @default.
- W2140661454 cites W2149364340 @default.
- W2140661454 cites W2152605969 @default.
- W2140661454 cites W2159900821 @default.
- W2140661454 cites W2160141505 @default.
- W2140661454 cites W2163300568 @default.
- W2140661454 cites W2164778558 @default.
- W2140661454 cites W2165688465 @default.
- W2140661454 cites W2166500502 @default.
- W2140661454 cites W2167288815 @default.
- W2140661454 cites W2169875798 @default.
- W2140661454 cites W2213203705 @default.
- W2140661454 cites W2313201345 @default.
- W2140661454 cites W2398254184 @default.
- W2140661454 cites W2440205103 @default.
- W2140661454 doi "https://doi.org/10.1093/hmg/ddt596" @default.
- W2140661454 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3959814" @default.
- W2140661454 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24271013" @default.
- W2140661454 hasPublicationYear "2013" @default.
- W2140661454 type Work @default.
- W2140661454 sameAs 2140661454 @default.