N-butylidenephthalide attenuates Alzheimer's disease-like cytopathy in Down syndrome induced pluripotent stem cell-derived neurons

Scientific Reports
Chia-Yu ChangHong-Lin Su

Abstract

Down syndrome (DS) patients with early-onset dementia share similar neurodegenerative features with Alzheimer's disease (AD). To recapitulate the AD cell model, DS induced pluripotent stem cells (DS-iPSCs), reprogrammed from mesenchymal stem cells in amniotic fluid, were directed toward a neuronal lineage. Neuroepithelial precursor cells with high purity and forebrain characteristics were robustly generated on day 10 (D10) of differentiation. Accumulated amyloid deposits, Tau protein hyperphosphorylation and Tau intracellular redistribution emerged rapidly in DS neurons within 45 days but not in normal embryonic stem cell-derived neurons. N-butylidenephthalide (Bdph), a major phthalide ingredient of Angelica sinensis, was emulsified by pluronic F127 to reduce its cellular toxicity and promote canonical Wnt signaling. Interestingly, we found that F127-Bdph showed significant therapeutic effects in reducing secreted Aβ40 deposits, the total Tau level and the hyperphosphorylated status of Tau in DS neurons. Taken together, DS-iPSC derived neural cells can serve as an ideal cellular model of DS and AD and have potential for high-throughput screening of candidate drugs. We also suggest that Bdph may benefit DS or AD treatment by sca...Continue Reading

References

Jun 1, 1989·The New England Journal of Medicine·B RumbleC L Masters
Jun 1, 1986·Brain Research Bulletin·J T CoyleJ D Gearhart
Oct 1, 1984·Chemical & Pharmaceutical Bulletin·S MiyazakiM Takada
Aug 2, 1996·The Journal of Biological Chemistry·D J Selkoe
Jul 1, 1996·Human Molecular Genetics·R SherringtonP H St George-Hyslop
Jan 9, 2001·Journal of Neurochemistry·H F DoveyJ E Audia
Aug 21, 2003·Progress in Neurobiology·Paul R TurnerWickliffe C Abraham
Jun 15, 2004·Experimental Cell Research·Alejandra R AlvarezNibaldo C Inestrosa
Jul 2, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Andrea CaricasoleFerdinando Nicoletti
Aug 24, 2004·Nature Cell Biology·Kuang-Hueih ChenJian Tang
Apr 14, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Todd D Gould, Husseini K Manji
Oct 3, 2006·Brain : a Journal of Neurology·Katharina BuergerHarald Hampel
Mar 29, 2007·The Journal of Biological Chemistry·Kengo UemuraAyae Kinoshita
Aug 9, 2007·Nature Reviews. Neuroscience·Carlo BallatoreJohn Q Trojanowski
Dec 20, 2007·Journal of Neurochemistry·Claudie HooperSimon Lovestone
Feb 1, 2008·The Journal of Biological Chemistry·Margaret H MagdesianSérgio T Ferreira
Aug 12, 2008·Cell·In-Hyun ParkGeorge Q Daley
Sep 4, 2008·Reproductive Biomedicine Online·En-Hui ChengMaw-Sheng Lee
Mar 20, 2009·Human Molecular Genetics·Frances K WisemanElizabeth M C Fisher
Jan 7, 2010·Journal of Neurochemistry·Maria Cristina RosiFiorella Casamenti
Jun 18, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ying PengCynthia A Lemere
Jan 27, 2012·Nature·Mason A IsraelLawrence S B Goldstein
May 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jason P WeickAnita Bhattacharyya
Feb 20, 2014·Journal of Molecular Cell Biology·Nibaldo C Inestrosa, Lorena Varela-Nallar

❮ Previous
Next ❯

Citations

Jan 29, 2016·Nature Reviews. Molecular Cell Biology·Yishai AviorNissim Benvenisty
Nov 4, 2015·Frontiers in Behavioral Neuroscience·Xun Yu ChoongElizabeth M C Fisher
Aug 6, 2015·Nature Reviews. Neuroscience·Frances K WisemanAndré Strydom
Mar 24, 2017·Cell Death & Disease·V C JonesL Mohamet
Feb 1, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hsiao-Chien TingHorng-Jyh Harn
Feb 2, 2018·International Journal of Molecular Sciences·Hueng-Chuen FanHorng-Jyh Harn
Aug 14, 2018·Current Drug Targets·Duraiswamy BasavanMohan K S Kumar
Sep 22, 2018·Molecular Neurobiology·Kuo-Hsuan ChangChiung-Mei Chen
Jun 7, 2019·World Journal of Stem Cells·Kate Elizabeth Hawkins, Michael Duchen
Feb 23, 2020·International Journal of Molecular Sciences·Wei WuliHorng-Jyh Harn
Aug 9, 2019·Molecular Psychiatry·Jay PenneyLi-Huei Tsai
Jun 15, 2017·Alzheimer's Research & Therapy·Charles ArberSelina Wray
Apr 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chia-Yu ChangTsung-Jung Ho
Feb 8, 2019·Journal of Biomedical Science·Fernanda MajoloJaderson Costa Da Costa
Dec 17, 2020·Neuropsychiatric Disease and Treatment·Yuan Wang, Miao Peng
Feb 4, 2021·International Journal of Molecular Sciences·Lu Qian, Julia Tcw
Feb 10, 2021·The Journal of Pharmacology and Experimental Therapeutics·Zizhen Si, Xidi Wang
Aug 8, 2021·International Journal of Molecular Sciences·Dorit TrudlerStuart A Lipton

❮ Previous
Next ❯

Methods Mentioned

BETA
scraping
ELISA
dynamic light scattering
transfection
nuclear translocation

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.