Isolation and partial characterization of ovine lactoferrin.

Ovine lactoferrin was isolated by ammonium sulfate precipitation and ion exchange chromatography. Comparative analyses were performed with the bovine protein. Differences in the amino acid compositions and the tertiary structure of the proteins were observed.     

Isolation and partial characterization of ovine lactoferrin

Summary Ovine lactoferrin was isolated by ammonium sulfate precipitation and ion exchange chromatography. Comparative analyses were performed with the bovine protein. Differences in the amino acid compositions and the tertiary structure of the proteins were observed.Acknowledgments. We would like to thank Dr M. Casey for his interest in this work, Dr P. Lavanchy for performing the amino acid analyses and M.F. Baumann for providing us with ewe milk.     

Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease

Huntington disease is one of nine inherited neurodegenerative disorders caused by a polyglutamine tract expansion. Expanded polyglutamine proteins accumulate abnormally in intracellular aggregates. Here we show that mammalian target of rapamycin (mTOR) is sequestered in polyglutamine aggregates in cell models, transgenic mice and human brains. Sequestration of mTOR impairs its kinase activity and induces autophagy, a key clearance pathway for mutant huntingtin fragments. This protects against polyglutamine toxicity, as the specific mTOR inhibitor rapamycin attenuates huntingtin accumulation and cell death in cell models of Huntington disease, and inhibition of autophagy has the converse effects. Furthermore, rapamycin protects against neurodegeneration in a fly model of Huntington disease, and the rapamycin analog CCI-779 improved performance on four different behavioral tasks and decreased aggregate formation in a mouse model of Huntington disease. Our data provide proof-of-principle for the potential of inducing autophagy to treat Huntington disease.