کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
330836 1433608 2011 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
β-Amyloid impairs axonal BDNF retrograde trafficking
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
β-Amyloid impairs axonal BDNF retrograde trafficking
چکیده انگلیسی

The neurotrophin, brain-derived neurotrophic factor (BDNF), is essential for synaptic function, plasticity and neuronal survival. At the axon terminal, when BDNF binds to its receptor, tropomyosin-related kinase B (TrkB), the signal is propagated along the axon to the cell body, via retrograde transport, regulating gene expression and neuronal function. Alzheimer disease (AD) is characterized by early impairments in synaptic function that may result in part from neurotrophin signaling deficits. Growing evidence suggests that soluble β-amyloid (Aβ) assemblies cause synaptic dysfunction by disrupting both neurotransmitter and neurotrophin signaling. Utilizing a novel microfluidic culture chamber, we demonstrate a BDNF retrograde signaling deficit in AD transgenic mouse neurons (Tg2576) that can be reversed by γ-secretase inhibitors. Using BDNF-GFP, we show that BDNF-mediated TrkB retrograde trafficking is impaired in Tg2576 axons. Furthermore, Aβ oligomers alone impair BDNF retrograde transport. Thus, Aβ reduces BDNF signaling by impairing axonal transport and this may underlie the synaptic dysfunction observed in AD.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 32, Issue 5, May 2011, Pages 821–833
نویسندگان
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