ß-Amyloid impairs axonal BDNF retrograde trafficking.
Neurobiol Aging
; 32(5): 821-33, 2011 May.
Article
en En
| MEDLINE
| ID: mdl-19540623
ABSTRACT
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 ß-amyloid (Aß) 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, Aß oligomers alone impair BDNF retrograde transport. Thus, Aß reduces BDNF signaling by impairing axonal transport and this may underlie the synaptic dysfunction observed in AD.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Axones
/
Transporte Axonal
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Péptidos beta-Amiloides
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Factor Neurotrófico Derivado del Encéfalo
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Enfermedad de Alzheimer
Límite:
Animals
Idioma:
En
Revista:
Neurobiol Aging
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos