Mitochondrial Disease: Neuronal Defects in Cell Culture

线粒体基因组缺陷(Mtdna)是临床上重要的神经系统疾病的一个重要原因。 疾病。尽管有这种认识，而且线粒体基因组很小，但潜在的疾病 机制仍不确定。因此，尽管诊断是可能的，但临床医生很难提供更多 而不是对病人的有限帮助。该项目旨在阐明线粒体DNA突变和 通过第一次对近端进行彻底检查而导致的神经紊乱 缺陷发生在神经元本身。这将通过在 人，成人来源的胚胎癌细胞(不是胚胎干细胞)，从而建立一种 培养的人源性神经元线粒体紊乱的模型系统。细胞缺陷的细胞 神经元的特征将通过分析发育，神经递质表达，电生理， 细胞死亡敏感性和神经元的生物能量学。希望，关于特定缺陷的知识在 细胞水平将为线粒体呼吸链障碍的治疗提供更好的靶向。

Defects in the mitochondrial genome (mtDNA) are a significant cause of clinically important neurological disease. Despite this recognition and the small size of the mitochondrial genome, the underlying disease mechanisms remain uncertain. Thus, though diagnosis is possible, it is difficult for clinicians to offer more than limited help to patients. This project aims to elucidate the connection between a mtDNA mutation and the resulting neurological disorder by undertaking, for the first time, a thorough examination of the proximal defects occurring within the neurons themselves. This will be done by creating transmitochondrial cybrids in human, adult-derived embryonal carcinoma cells (not embryonicstem cells) and thereby establishing a model system of mitochondrial disorders in human-derived, cultured neurons. The cellular defects of the neurons will be characterized by analyzing the development, neurotransmitter expression, electrophysiology, cell death sensitivity, and bioenergetics of the neurons. Hopefully, the knowledge of the specific defects at the cellular level will allow better targeting for therapy of disorders of the mitochondrial respiratory chain.