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Proc Natl Acad Sci U S A,
2003]
The most common neurodegenerative diseases are characterized by the presence of abnormal filamentous protein inclusions in nerve cells of the brain. In Alzheimer's disease, these inclusions are made of hyperphosphorylated tau protein. Together with the extracellular beta-amyloid deposits, they consitute the defining neuropathological characteristics of Alzheimer's disease. Tau inclusions, in the absence of extracellular deposits, are characteristic of progressive supranuclear palsy, corticobasal degeneration, Pick's disease, argyrophilic grain disease, and frontotemporal dementia and parkinsonism linked to chromosome 17. The identification of mutations in Tau in FTDP-17 has established that dysfunction of tau protein is central to the neurodegenerative process. At an experimental level, the expression of mutant human tau in nerve cells is leading to improved models of neurodegeneration. In this issue of PNAS, Kraemer et al. describe lines of Caenorhabditis elegans expressing transgenic wild-type and mutant human tau protein. They represent an important addition to
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Proc Natl Acad Sci U S A,
2003]
The discovery of transgene silencing in plants and double-stranded RNA (dsRNA) interference in the worm Caenorhabditis elegans has led to the latest revolution in molecular biology, RNA interference (RNAi). Over 10 years ago it was noted that several transgenic plant lines each containing the same ectopic transgene not only failed to be expressed but also inhibited the expression of the endogenous gene. Similarly, a determined Craig Mello and Andy Fire, attempting to reduce gene function using using antisense RNA in the worm, discovered a minor contaminant in their antisense RNA preparation effectively and repeatedly reduced expression of the endogenous gene. In both cases, dsRNA homologous to the gene of interest was responsible for these observations. In the last 4 years, these discoveries have been extended to include protozoa,