Institute of Molecular Biosciences, Department of Microbiology, Karl-Franzens-University of Graz, Graz, Austria.
Trends Biochem Sci. 2010 Mar;35(3):135-44. doi: 10.1016/j.tibs.2009.10.005. Epub 2009 Nov 18.
Neurodegeneration is characterized by the disease-specific loss of neuronal activity, culminating in the irreversible destruction of neurons. Neuronal cell death can proceed via distinct subroutines such as apoptosis and necrosis, but the underlying molecular mechanisms remain poorly understood. Saccharomyces cerevisiae is an established model for programmed cell death, characterized by distinct cell death pathways conserved from yeast to mammals. Recently, yeast models for several major classes of neurodegeneration, namely alpha-synucleinopathies, polyglutamine disorders, beta-amyloid diseases, tauopathies, and TDP-43 proteinopathies, have been established. Heterologous expression of the human proteins implicated in these disorders has unraveled important insights in their detrimental function, pointing to ways in which yeast might advance the mechanistic dissection of cell death pathways relevant for human neurodegeneration.
神经退行性病变的特征是神经元活动的疾病特异性丧失，最终导致神经元的不可逆转破坏。神经元细胞死亡可以通过不同的程序进行，如凋亡和坏死，但潜在的分子机制仍知之甚少。酿酒酵母是程序性细胞死亡的成熟模型，其特征是从酵母到哺乳动物都保守的不同细胞死亡途径。最近，几种主要神经退行性疾病的酵母模型，即α-突触核蛋白病、多聚谷氨酰胺病、β-淀粉样蛋白病、tau 病和 TDP-43 蛋白病，已经建立。这些疾病中涉及的人类蛋白的异源表达揭示了其有害功能的重要见解，指出了酵母在人类神经退行性疾病相关细胞死亡途径的机制解析方面可能取得的进展。
