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Effects of synaptic activity modulation in beta-amyloid homeostasis and Alzheimer's disease| old_uid | 11613 |
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| title | Effects of synaptic activity modulation in beta-amyloid homeostasis and Alzheimer's disease |
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| start_date | 2012/07/11 |
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| schedule | 11h30 |
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| online | no |
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| location_info | Bât. B, 4e étage, salle 501 |
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| summary | In Alzheimer’s disease (AD) patients the best pathologic correlate of cognitive impairment is loss of synapses more than amyloid plaques, neurofibrillary tangles or loss of neurons (Terry et al., 1991). The recent discovery that synaptic activity itself can have an effect on amyloid-Beta (ABeta) represented a breakthrough in AD research: synaptic activity enhances neuronal secretion of ABeta in vitro and in vivo (Kamenetz et al., 2003; Cirrito et al., 2005).
Our group demonstrated that synaptic activity also affects intraneuronal ABeta, a pool of ABeta that appears at very early stages of AD, precedes the appearance of amyloid plaques (Mori et al., 2002; Oddo et al., 2003), and is associated with subcelluar pathology (Takahashi et al., 2002). Synaptic activation reduces levels of intraneuronal ABeta and protects synapses (Tampellini et al., 2009). Activity-induced intraneuronal ABeta42 clearance requires neprilysin (Tampellini et al., 2009; Tampellini et al., 2011), the main ABeta-degrading enzyme (Iwata et al., 2000). On the other hand, synaptic inhibition increases intraneuronal ABeta42, exacerbates memory impairment and loss of synapses despite reduced plaque deposition (Tampellini et al., 2010), suggesting a protective role of synaptic activation in AD. |
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| responsibles | Wehrle |
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