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- W1966445049 abstract "Tau is known to be a key factor in the pathogenesis of various neurodegenerative diseases, categorized as tauopathy. Because the severity of tau pathology links closely to that of neuron loss and the extent of clinical symptom, it is likely that the elucidation of the mechanism underlying tauopathy leads us to the development of tau therapeutics. For this purpose, the animal model is required, which is appropriate for the analysis of tau-neurotoxicity and the drug screening. We developed novel transgenic nematode (C. elegans) models expressing wild-type or FTDP-17 mutant (P301L and R406W) tau in all neurons at various expression levels using unc-119 promoter, and subjected them to behavioral and biochemical studies. For morphological study, tau-expressing worms were crossbred with pan-neuronal DsRed expressing line. Chemical compounds to be tested were directly administrated onto NGM culture plates. Uncoordinated movement (unc) appeared even in wild-type tau-expressing worms, which was found in an expression level-dependent manner. Neuritic abnormalities are associated with the behavioral deficit. Similar extents of behavioral and morphological abnormalities were found in R406W tau-expressing animal even in its lowest expression level that does not cause uncoordination in case of wild-type tau. Thus, the tau neurotoxicity depends on its expression level, and FTDP-17 mutation likely enhances its toxicity. Biochemical studies showed that the expressed tau was phosphorylated to a similar extent of PHF-tau, but was not fractionated into RIPA-insoluble aggregates. This suggests that the tau causes neuronal dysfunction without insoluble aggregate formation. We also found the curcumin, a major phytochemical compound in turmeric, improves not only uncoordination but also reduces neuritic abnormalities in wild-type and R406W mutant tau-expressing nematodes. Methylene blue and treharose, both previously reported to have potent anti-aggregation effects, had no favorable effect. Altogether, it is likely that curcumin improves tau-induced neuronal dysfunction independent of interference with tau aggregation step." @default.
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- W1966445049 date "2010-07-01" @default.
- W1966445049 modified "2023-10-02" @default.
- W1966445049 title "P4‐026: Curcumin Improves Tau‐mediated Neuronal Dysfunction in Nematode" @default.
- W1966445049 doi "https://doi.org/10.1016/j.jalz.2010.08.086" @default.
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