Patient-derived iPSC modeling of rare neurodevelopmental disorders: Molecular pathophysiology and prospective therapies.
Patient-derived iPSC modeling of rare neurodevelopmental disorders: Molecular pathophysiology and prospective therapies.
复制标题
罕见神经发育障碍的患者源性IPSC模型：分子病理生理学和前瞻性治疗。
DOI：
10.1016/j.neubiorev.2020.12.025
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发表时间：
2021-03
影响因子：
8.2
通讯作者：
Upadhya D
中科院分区：
文献类型：
--
作者：
Sabitha KR;Shetty AK;Upadhya D
由于遗传和获得性因素，在早期胚胎发育期间表现出的病理学改变引发各种神经发育障碍（NDD）。除了主要的NDD，还有几种罕见的NDD，表现出特定的特征和不同程度的严重程度，由于遗传和表观遗传异常触发。受试者的稀少，用于详细分析的神经组织的缺乏，以及疾病特异性动物模型的不可用，阻碍了对罕见NDD的详细理解，直到十年前才对医学和科学界提出了更高的挑战。通过患者来源的iPSC、CRISPR/Cas9技术和3D脑类器官模型的定向分化方案产生功能性神经元和神经胶质，为解码由单基因和多基因疾病引起的罕见NDD的脑发育病因提供了极好的机会和充满活力的资源。本综述确定了从患者来源的iPSC中证明的细胞和分子表型，以及为这些疾病确定的可能的治疗机会。新的见解，以加强现有的知识，这些疾病的病理生理学和前瞻性的治疗应用进行了讨论。
The pathological alterations that manifest during the early embryonic development due to inherited and acquired factors trigger various neurodevelopmental disorders (NDDs). Besides major NDDs, there are several rare NDDs, exhibiting specific characteristics and varying levels of severity triggered due to genetic and epigenetic anomalies. The rarity of subjects, paucity of neural tissues for detailed analysis, and the unavailability of disease-specific animal models have hampered detailed comprehension of rare NDDs, imposing heightened challenge to the medical and scientific community until a decade ago. The generation of functional neurons and glia through directed differentiation protocols for patient-derived iPSCs, CRISPR/Cas9 technology, and 3D brain organoid models have provided an excellent opportunity and vibrant resource for decoding the etiology of brain development for rare NDDs caused due to monogenic as well as polygenic disorders. The present review identifies cellular and molecular phenotypes demonstrated from patient-derived iPSCs and possible therapeutic opportunities identified for these disorders. New insights to reinforce the existing knowledge of the pathophysiology of these disorders and prospective therapeutic applications are discussed.
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影响因子：
23.9
作者：
Bershteyn M;Nowakowski TJ;Pollen AA;Di Lullo E;Nene A;Wynshaw-Boris A;Kriegstein AR
通讯作者：
Kriegstein AR
影响因子：
3.6
作者：
Andoh-Noda T;Akamatsu W;Miyake K;Matsumoto T;Yamaguchi R;Sanosaka T;Okada Y;Kobayashi T;Ohyama M;Nakashima K;Kurosawa H;Kubota T;Okano H
通讯作者：
Okano H
影响因子：
5
作者：
Ando, Shiori;Funato, Michinori;Hara, Hideaki
通讯作者：
Hara, Hideaki
影响因子：
4.4
作者：
Burglen, L;Lefebvre, S;Melki, J
通讯作者：
Melki, J
影响因子：
6.2
作者：
Breen, Michael S.;Browne, Andrew;Drapeau, Elodie
通讯作者：
Drapeau, Elodie