來自英國愛丁堡大學、倫敦大學國王學院,、美國哥倫比亞大學和舊金山大學的科學家們利用前沿干細胞研究方法取得一項研究突破,，從而可能會加快人們開發(fā)出治療運動神經(jīng)元疾病(motor neurone disease, MND)的新方法。
中國細胞生物學學會干細胞生物學分會2012年春季會議
他們從一名患有遺傳性MND疾病的病人身上提取皮膚細胞,，并利用提取到的皮膚細胞構(gòu)建出運動神經(jīng)元,。
他們證實在90%以上的MND病例中發(fā)現(xiàn)的蛋白TDP-43異常導致運動神經(jīng)元死亡,。這也是科學家們首次能夠觀察到蛋白TDP-43異常直接對人運動神經(jīng)元產(chǎn)生影響,。相關研究結(jié)果于2012年3月26日發(fā)表在PNAS期刊上。
MND疾病是一種破壞性的,、不可治療的和最終致命性的疾病,，是由于控制運動、語言和呼吸的運動神經(jīng)元的漸近性丟失而導致的,。
愛丁堡大學教授Siddharthan Chandran說,，“利用病人干細胞在盤碟中構(gòu)建MND疾病模型有助于我們研究這種可怕疾病的病因以及加快藥物開發(fā)。” (生物谷：towersimper編譯)
doi:10.1073/pnas.1202922109
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Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability
Bilada Bilican, Andrea Serio, Sami J. Barmada, Agnes Lumi Nishimura, Gareth J. Sullivan, Monica Carrasco, Hemali P. Phatnani, Clare A. Puddifoot, David Story, Judy Fletcher, In-Hyun Park, Brad A. Friedman, George Q. Daley, David J. A. Wyllie, Giles E. Hardingham, Ian Wilmut, Steven Finkbeiner, Tom Maniatis, Christopher E. Shaw, and Siddharthan Chandran
Transactive response DNA-binding (TDP-43) protein is the dominant disease protein in amyotrophic lateral sclerosis (ALS) and a subgroup of frontotemporal lobar degeneration (FTLD-TDP). Identification of mutations in the gene encoding TDP-43 (TARDBP) in familial ALS confirms a mechanistic link between misaccumulation of TDP-43 and neurodegeneration and provides an opportunity to study TDP-43 proteinopathies in human neurons generated from patient fibroblasts by using induced pluripotent stem cells (iPSCs). Here, we report the generation of iPSCs that carry the TDP-43 M337V mutation and their differentiation into neurons and functional motor neurons. Mutant neurons had elevated levels of soluble and detergent-resistant TDP-43 protein, decreased survival in longitudinal studies, and increased vulnerability to antagonism of the PI3K pathway. We conclude that expression of physiological levels of TDP-43 in human neurons is sufficient to reveal a mutation-specific cell-autonomous phenotype and strongly supports this approach for the study of disease mechanisms and for drug screening.
