Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.celrep.2020.107839
Title: Caspase Activation and Caspase-Mediated Cleavage of APP Is Associated with Amyloid ?-Protein-Induced Synapse Loss in Alzheimer's Disease
Authors: Park, G.
Nhan, H.S.
Tyan, S.-H.
Kawakatsu, Y.
Zhang, C.
Navarro, M.
Koo, E.H. 
Keywords: Alzheimer's disease
APP
APP C31
caspase
synaptic injury
Issue Date: 2020
Publisher: Elsevier B.V.
Citation: Park, G., Nhan, H.S., Tyan, S.-H., Kawakatsu, Y., Zhang, C., Navarro, M., Koo, E.H. (2020). Caspase Activation and Caspase-Mediated Cleavage of APP Is Associated with Amyloid ?-Protein-Induced Synapse Loss in Alzheimer's Disease. Cell Reports 31 (13) : 107839. ScholarBank@NUS Repository. https://doi.org/10.1016/j.celrep.2020.107839
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
Abstract: Amyloid ?-protein (A?) toxicity is hypothesized to play a seminal role in Alzheimer's disease (AD) pathogenesis. However, it remains unclear how A? causes synaptic dysfunction and synapse loss. We hypothesize that one mechanism of A?-induced synaptic injury is related to the cleavage of amyloid ? precursor protein (APP) at position D664 by caspases that release the putatively cytotoxic C31 peptide. In organotypic slice cultures derived from mice with a knock-in mutation in the APP gene (APP D664A) to inhibit caspase cleavage, A?-induced synaptic injury is markedly reduced in two models of A? toxicity. Loss of dendritic spines is also attenuated in mice treated with caspase inhibitors. Importantly, the time-dependent dendritic spine loss is correlated with localized activation of caspase-3 but is absent in APP D664A cultures. We propose that the APP cytosolic domain plays an essential role in A?-induced synaptic damage in the injury pathway mediated by localized caspase activation. � 2020 The AuthorsPark et al. show that inhibition of amyloid precursor protein (APP) C terminus cleavage by D664A mutation prevents A?-induced local caspase activation, leading to localized synaptic injury. � 2020 The Authors
Source Title: Cell Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/197703
ISSN: 22111247
DOI: 10.1016/j.celrep.2020.107839
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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