Prenatal neurogenesis induction therapy normalizes brain structure and function in Down syndrome mice

Nakano-Kobayashi Akiko; Awaya Tomonari; Kii IsaoSumida YutoOkuno YukikoYoshida SuguruSumida TomoeInoue HaruhisaHosoya TakamitsuHagiwara Masatoshi

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Prenatal neurogenesis induction therapy normalizes brain structure and function in Down syndrome mice

机译：Prenatal neurogenesis induction therapy normalizes brain structure and function in Down syndrome mice

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Down syndrome (DS) caused by trisomy of chromosome 21 is the most common genetic cause of intellectual disability. Although the prenatal diagnosis of DS has become feasible, there are no therapies available for the rescue of DS-related neurocognitive impairment. A growth inducer newly identified in our screen of neural stem cells (NSCs) has potent inhibitory activity against dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) and was found to rescue proliferative deficits in Ts65Dn-derived neurospheres and human NSCs derived from individuals with DS. The oral administration of this compound, named ALGERNON (altered generation of neurons), restored NSC proliferation in murine models of DS and increased the number of newborn neurons. Moreover, administration of ALGERNON to pregnant dams rescued aberrant cortical formation in DS mouse embryos and prevented the development of abnormal behaviors in DS offspring. These data suggest that the neurogenic phenotype of DS can be prevented by ALGERNON prenatal therapy.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2017年第38期|10268-10273|共6页
作者
Nakano-Kobayashi Akiko; Awaya Tomonari; Kii IsaoSumida YutoOkuno YukikoYoshida SuguruSumida TomoeInoue HaruhisaHosoya TakamitsuHagiwara Masatoshi;
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作者单位

Kyoto Univ, Grad Sch Med, Med Res Support Ctr, Kyoto 6068501, Japan;

Tokyo Med & Dent Univ, Inst Biomats & Bioengn, Lab Chem Biosci, Tokyo 1010062, Japan;

Kyoto Univ, Ctr iPS Cell Res & Applicat, Kyoto 6068507, JapanKyoto Univ, Grad Sch Med, Dept Anat & Dev Biol, Kyoto 6068501, Japan;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
developmental disorder; Down syndrome; neurogenesis;

Prenatal neurogenesis induction therapy normalizes brain structure and function in Down syndrome mice

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