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为了一项事业而献身:无脊椎动物遗传学研究人类神经退行性疾病

Dying for a cause: invertebrate genetics takes on human neurodegeneration.

作者信息

Driscoll Monica, Gerstbrein Beate

机构信息

Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, A232 Nelson Biological Laboratories, 604 Allison Road, Piscataway, New Jersey 08855, USA.

出版信息

Nat Rev Genet. 2003 Mar;4(3):181-94. doi: 10.1038/nrg1018.

Abstract

If invertebrate neurons are injured by hostile environments or aberrant proteins they die much like human neurons, indicating that the powerful advantages of invertebrate molecular genetics might be successfully used for testing specific hypotheses about human neurological diseases, for drug discovery and for non-biased screens for suppressors and enhancers of neurodegeneration. Recent molecular dissection of the genetic requirements for hypoxia, excitotoxicity and death in models of Alzheimer disease, polyglutamine-expansion disorders, Parkinson disease and more, is providing mechanistic insights into neurotoxicity and suggesting new therapeutic interventions. An emerging theme is that neuronal crises of distinct origins might converge to disrupt common cellular functions, such as protein folding and turnover.

摘要

如果无脊椎动物的神经元受到恶劣环境或异常蛋白质的损伤,它们的死亡方式与人类神经元非常相似,这表明无脊椎动物分子遗传学的强大优势可能会成功用于检验关于人类神经疾病的特定假说、药物研发以及对神经退行性变的抑制因子和增强因子进行无偏差筛选。最近对阿尔茨海默病、多聚谷氨酰胺扩增性疾病、帕金森病等模型中缺氧、兴奋性毒性和死亡的遗传需求进行的分子剖析,正在为神经毒性提供机制性见解,并提示新的治疗干预措施。一个新出现的主题是,不同起源的神经元危机可能会汇聚在一起,破坏诸如蛋白质折叠和周转等共同的细胞功能。

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