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BACE1 Inhibition in AD Therapy and its Potential Side Effects| old_uid | 14460 |
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| title | BACE1 Inhibition in AD Therapy and its Potential Side Effects |
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| start_date | 2017/10/16 |
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| schedule | 12h |
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| online | no |
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| location_info | Bât. IDEE Entrée Est (accès Bd Laurent Bonnevay), Amphithéâtre Margaux Hemingway |
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| details | Cycle des conférences 2017 |
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| summary | As the key protease of Aß production, Beta-site amyloid precursor protein cleaving enzyme 1
(BACE1) is a promising drug target for the treatment of Alzheimer’s disease (AD). However,
we have recently shown that prolonged inhibition of BACE1 interfers with
structural and functional synaptic plasticity (Filser et al. Biol. Psych 2015), most likely due to the diminished processing of physiological BACE1 substrates. Seizure protein 6 (Sez6) is exclusively processed
by BACE1 and it is required for normal dendritic arborization and spine maintenance.
Interestingly, the side effect of BACE1 inhibitor was not observed in chronically treated Sez6
knockout mice, suggesting that Sez6 is critically involved in these BACE1 inhibitor
-
mediated
synaptic alterations. Encouragingly, we also observed that BACE1 inhibitor treatment in a
transgenic AD mouse model (APPPS1) reduced amyloid plaque formation as well as growth, and ameliorated the plaque associated synaptic and axonal pathology. In conclusion, our results suggest that
an adequate inhibitor dosage for the treatment of AD might be identified
to balances both clinical safety and efficacy. |
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| responsibles | CRNL |
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