Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
Localization, induction, and cellular effects of tau phosphorylated at threonine 217.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Rajbanshi Binita, Guruacharya Anuj, Mandell James W, Bloom George S
Аннотация
INTRODUCTION: Tau phosphorylation at T217 is a promising Alzheimer's disease (AD) biomarker, but its functional consequences were unknown.
METHODS: Human brain and cultured mouse neurons were analyzed by immunoblotting and immunofluorescence for total tau, taupT217 , taupT181 , taupT231 , and taupS396/pS404 . Direct stochastic optical reconstruction microscopy (dSTORM) super resolution microscopy was used to localize taupT217 in cultured neurons. Enhanced green fluorescent protein (EGFP)-tau was expressed in fibroblasts as wild type and T217E pseudo-phosphorylated tau, and fluorescence recovery after photobleaching (FRAP) reported tau turnover rates on microtubules.
RESULTS: In the brain, taupT217 appears in neurons at Braak stages I and II, becomes more prevalent later, and co-localizes partially with other phospho-tau epitopes. In cultured neurons, taupT217 is increased by extracellular tau oligomers (xcTauOs) and is associated with developing post-synaptic sites. FRAP recovery was fastest for EGFP-tauT217E .
CONCLUSION: TaupT217 increases in the brain as AD progresses and is induced by xcTauOs. Post-synaptic taupT217 suggests a role for T217 phosphorylation in synapse impairment. T217 phosphorylation reduces tau's affinity for microtubules.
HIGHLIGHTS: Validation of anti-tau phosphorylated at threonine-217 (taupT217 ) specificity is essential due to epitope redundancy. taupT217 increases as Alzheimer's disease progresses and is found throughout diseased neurons. taupT217 is associated with developing post-synaptic sites in cultured neurons. Extracellular oligomers of tau, but not amyloid beta, increase intracellular taupT217 . T217E pseudo-phosphorylation reduces tau's affinity for microtubules.
METHODS: Human brain and cultured mouse neurons were analyzed by immunoblotting and immunofluorescence for total tau, taupT217 , taupT181 , taupT231 , and taupS396/pS404 . Direct stochastic optical reconstruction microscopy (dSTORM) super resolution microscopy was used to localize taupT217 in cultured neurons. Enhanced green fluorescent protein (EGFP)-tau was expressed in fibroblasts as wild type and T217E pseudo-phosphorylated tau, and fluorescence recovery after photobleaching (FRAP) reported tau turnover rates on microtubules.
RESULTS: In the brain, taupT217 appears in neurons at Braak stages I and II, becomes more prevalent later, and co-localizes partially with other phospho-tau epitopes. In cultured neurons, taupT217 is increased by extracellular tau oligomers (xcTauOs) and is associated with developing post-synaptic sites. FRAP recovery was fastest for EGFP-tauT217E .
CONCLUSION: TaupT217 increases in the brain as AD progresses and is induced by xcTauOs. Post-synaptic taupT217 suggests a role for T217 phosphorylation in synapse impairment. T217 phosphorylation reduces tau's affinity for microtubules.
HIGHLIGHTS: Validation of anti-tau phosphorylated at threonine-217 (taupT217 ) specificity is essential due to epitope redundancy. taupT217 increases as Alzheimer's disease progresses and is found throughout diseased neurons. taupT217 is associated with developing post-synaptic sites in cultured neurons. Extracellular oligomers of tau, but not amyloid beta, increase intracellular taupT217 . T217E pseudo-phosphorylation reduces tau's affinity for microtubules.