Université de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France.
Université de Strasbourg, CNRS, INSERM, Celphedia, Phenomin-Institut Clinique de la Souris (ICS), 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France.
Genes (Basel). 2021 Nov 20;12(11):1833. doi: 10.3390/genes12111833.
Down syndrome is the main cause of intellectual disabilities with a large set of comorbidities from developmental origins but also that appeared across life span. Investigation of the genetic overdosage found in Down syndrome, due to the trisomy of human chromosome 21, has pointed to one main driver gene, the Dyrk1a is a murine homolog of the drosophila gene. It has been found to be involved in many biological processes during development and in adulthood. Further analysis showed its haploinsufficiency in mental retardation disease 7 and its involvement in Alzheimer's disease. DYRK1A plays a role in major developmental steps of brain development, controlling the proliferation of neural progenitors, the migration of neurons, their dendritogenesis and the function of the synapse. Several strategies targeting the overdosage of DYRK1A in DS with specific kinase inhibitors have showed promising evidence that DS cognitive conditions can be alleviated. Nevertheless, providing conditions for proper temporal treatment and to tackle the neurodevelopmental and the neurodegenerative aspects of DS across life span is still an open question.
唐氏综合征是智力障碍的主要原因，其具有一系列源于发育起源的合并症，但也会在整个生命周期中出现。对唐氏综合征患者 21 号染色体三体性引起的基因超剂量的研究表明，有一个主要的驱动基因，即 Dyrk1a，它是果蝇基因的一种鼠类同源物。已经发现它在发育和成年期的许多生物过程中都有涉及。进一步的分析表明，它在智力障碍疾病 7 中的单倍不足和在阿尔茨海默病中的参与。 DYRK1A 在大脑发育的主要发育步骤中发挥作用，控制神经祖细胞的增殖、神经元的迁移、它们的树突发生和突触的功能。几种针对 DS 中 DYRK1A 超量的靶向策略，使用特定的激酶抑制剂，已经显示出有希望的证据表明，DS 的认知状况可以得到缓解。然而，为 DS 提供适当的时间治疗条件，并解决其整个生命周期中的神经发育和神经退行性方面的问题，仍然是一个悬而未决的问题。
