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Neuroprotective Activities of Heparin, Heparinase III, and Hyaluronic Acid on the Aβ42-Treated Forebrain Spheroids Derived from Human Stem Cells
journal contribution
posted on 2018-06-28, 00:00 authored by Julie Bejoy, Liqing Song, Zhe Wang, Qing-Xiang Sang, Yi Zhou, Yan LiExtracellular
matrix (ECM) components of the brain play complex
roles in neurodegenerative diseases. The study of microenvironment
of brain tissues with Alzheimer’s disease revealed colocalized
expression of different ECM molecules such as heparan sulfate proteoglycans
(HSPGs), chondroitin sulfate proteoglycans (CSPGs), matrix metalloproteinases
(MMPs), and hyaluronic acid. In this study, both cortical and hippocampal
populations were generated from human-induced pluripotent stem cell-derived
neural spheroids. The cultures were then treated with heparin (competes
for Aβ affinity with HSPG), heparinase III (digests HSPGs),
chondroitinase (digests CSPGs), hyaluronic acid, and an MMP-2/9 inhibitor
(SB-3CT) together with amyloid β (Aβ42) oligomers. The
results indicate that inhibition of HSPG binding to Aβ42 using
either heparinase III or heparin reduces Aβ42 expression and
increases the population of β-tubulin III+ neurons,
whereas the inhibition of MMP2/9 induces more neurotoxicity. The results
should enhance our understanding of the contribution of ECMs to the
Aβ-related neural cell death.
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β42 expressionHeparinase IIIdigesthippocampal populationsECM moleculesSB -3CTinhibitionβ- tubulin IIICSPGacidbrain tissuesheparinase IIIβ42-Treated Forebrain Spheroids Derivedneurodegenerative diseasescolocalized expressionNeuroprotective ActivitiesHuman Stem Cells Extracellular matrixβ affinityMMPheparan sulfate proteoglycansHSPG bindinghuman-induced pluripotentcell deathamyloid β
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