在2月28日《科學(xué)》（Science）雜志的在線版上，研究人員報(bào)道說,，已經(jīng)找到了一種與某些病例的肌萎縮性側(cè)索硬化（ALS,，也被稱為Lou Gehrig氏病）相關(guān)的罕見基因變異,。這些發(fā)現(xiàn)可能會幫助研究人員,，更多地了解這一致命的成年時起病的運(yùn)動神經(jīng)元疾病的發(fā)展過程。該疾病中有5-10%的病例是有遺傳性的（其他病例的發(fā)病原因尚不清楚）,。
Jemeen Sreedharan及其在英國和澳大利亞的同僚對英國的一個遺傳性ALS的大家族進(jìn)行了分析,。他們在一個叫做TDP-43的基因中發(fā)現(xiàn)了一種變異，而該變異看來與該疾病有關(guān),。研究人員在受ALS影響的神經(jīng)元中發(fā)現(xiàn)了團(tuán)簇狀的TDP-43蛋白,，而這些結(jié)果進(jìn)一步加強(qiáng)了TDP-43與該疾病之間的關(guān)聯(lián)性。
生物谷推薦原始出處：
（Science）,，DOI: 10.1126/science.1154584,，Jemeen Sreedharan，Christopher E. Shaw
TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
Jemeen Sreedharan , Ian P. Blair , Vineeta B. Tripathi , Xun Hu , Caroline Vance , Boris Rogelj , Steven Ackerley , Jennifer C. Durnall , Kelly L. Williams , Emanuele Buratti , Francisco Baralle , Jacqueline de Belleroche , J. Douglas Mitchell , P. Nigel Leigh , Ammar Al-Chalabi , Christopher C. Miller , Garth Nicholson , Christopher E. Shaw
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterised pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain and a mechanistic role in neurodegeneration remains speculative. We identified neighbouring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBPM337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP-43 fragmented more readily than wild-type in vitro and caused neural apoptosis and developmental delay in the chick embryo in vivo. Our evidence suggests a pathophysiological link between TDP-43 and ALS.
