Prion in yeast Huntington's disease
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《细胞学杂志》
Meriin et al., reporting on page 997, have developed the first yeast model for studying Huntington's disease. Yeast cannot undergo neurodegeneration, of course, but the simplicity and genetic manipulability of the system are already providing important mechanistic insights. The authors report that aggregation of a polypeptide with an expanded polyglutamine domain, mediated by a prion-like protein, is responsible for cell death in their system, suggesting revisions to earlier models of neurodegeneration.
In Huntington's disease, expansion of the huntingtin polyglutamine domain leads to protein aggregation in inclusion bodies and neuronal cell death. In some systems, however, long polyglutamine peptides are toxic without aggregating, suggesting that aggregation of mutant huntingtin might not determine toxicity. Meriin and colleagues found, however, that aggregation of long polyglutamine peptides in yeast correlated with toxicity. Mutations in certain chaperone genes, or curing the cells of the prion form of the Rnq1 protein, suppressed both aggregation and toxicity.
The results directly link polyglutamine peptide aggregation with cell death, and demonstrate that prion proteins are required for this process, at least in yeast. The evolutionary conservation of these mechanisms suggests that prion-like proteins might also be involved in mammalian polyglutamine expansion diseases.(AHuntingtin-like proteins make yeast sic)
In Huntington's disease, expansion of the huntingtin polyglutamine domain leads to protein aggregation in inclusion bodies and neuronal cell death. In some systems, however, long polyglutamine peptides are toxic without aggregating, suggesting that aggregation of mutant huntingtin might not determine toxicity. Meriin and colleagues found, however, that aggregation of long polyglutamine peptides in yeast correlated with toxicity. Mutations in certain chaperone genes, or curing the cells of the prion form of the Rnq1 protein, suppressed both aggregation and toxicity.
The results directly link polyglutamine peptide aggregation with cell death, and demonstrate that prion proteins are required for this process, at least in yeast. The evolutionary conservation of these mechanisms suggests that prion-like proteins might also be involved in mammalian polyglutamine expansion diseases.(AHuntingtin-like proteins make yeast sic)