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- W3021361140 abstract "Tau is a neuronal cytoskeletal protein, the most well characterised function of which is its binding to and stabilisation of microtubules, which serve as tracks for axonal transport in neurons. Abnormalities in tau have been linked to a number of neurodegenerative disorders including Alzheimer's disease (AD). In AD brain tau is the main constituent of neurofibrillary tangles, which are composed of paired helical filaments of insoluble tau. Tau in these inclusions is abnormally phosphorylated, although the mechanisms linking phosphorylation to the formation of aggregates remain unclear. Phosphorylation may induce aggregation by changing the physical properties of tau, or may mediate tangle formation through a change in other properties of tau such as its microtubule binding or axonal transport. To develop a method for the study of the axonal transport of tau in individual cultured neurons. To examine the effect of modulating tau phosphorylation on its axonal transport. cDNA constructs of enhanced green fluorescent protein (EGFP) tagged tau were transfected into primary cultures of rat cortical neurons and images of individual neurons were collected at different timepoints after transfection. The rate of transport of tau–EGFP was calculated by measuring the distance from the axon hilum to the front of EGFP fluorescence in individual neurons. We were able to track net anterograde axonal transport in individual live neurons over several hours in culture. The rate of tau transport was comparable both to that previously observed in vivo and in vitro. Metabolic inhibition using 2–deoxy–D–glucose and sodium azide inhibited transport of tau thus validating our experimental system. Treatment of neurons with agents affecting tau phosphorylation was found to modulate tau transport. We have developed and validated a novel method to determine the rate of axonal transport of tau in individual neurons in culture. This experimental system can be used to investigate the effects of modulators of tau phosphorylation on its transport." @default.
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- W3021361140 date "2006-07-01" @default.
- W3021361140 modified "2023-09-27" @default.
- W3021361140 title "P3-291: Real-time image acquisition to measure the effects of modulating phosphorylation on the overall rate of tau axonal transport in individual neurons" @default.
- W3021361140 doi "https://doi.org/10.1016/j.jalz.2006.05.1560" @default.
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