title: Caspase-12 activation is involved in amyloid-β protein-induced synaptic toxicity.
abstract: Synapse loss is considered to be the best correlate of cognitive impairments in Alzheimer's disease (AD), and growing evidence supports the notion that certain events that trigger neuronal death in AD can be initiated by the local activation of caspases within the synaptic compartment. We have demonstrated previously that presynaptic terminals are particularly vulnerable to endoplasmic-reticulum (ER)-stress depending of amyloid-β protein (Aβ). This toxicity included a notable reduction of actin and synaptophysin protein and mitochondrial dysfunction. This synaptic damage was prevented by incubation with a wide range of caspase inhibitor, suggesting the activation of local synaptic apoptotic mechanisms. The ER-resident caspase-12 was initially identified as a mediator of Aβ neurotoxicity. Thus, the current study was conducted to explore the presence and local activation of the caspase-12 in cortical and hippocampal synaptosomes isolated from rat and from the triple transgenic mouse model of AD (3xTg-AD) in the presence of Aβ and ryanodine. Under these conditions, we found mitochondrial failure accompanied by a reduction in actin levels which was dependent on caspase-12 activation suggesting its participation in Aβ-induced synaptic toxicity.
authors.affiliation: Departamento de Investigación Básica, Dirección de Investigación, Instituto de Geriatría, Institutos Nacionales de Salud, Secretaría de Salud, México, DF México.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Quiroz-Baez
authors.forename: Patricia
authors.initials: P
authors.lastname: Ferrera
authors.forename: Rigoberto
authors.initials: R
authors.lastname: Rosendo-Gutiérrez
authors.forename: Julio
authors.initials: J
authors.lastname: Morán
authors.forename: Federico
authors.initials: F
authors.lastname: Bermúdez-Rattoni
authors.forename: Clorinda
authors.initials: C
authors.lastname: Arias
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001797:Blood Protein Electrophoresis; D015153:Blotting, Western; D053454:Caspase 12 / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects* / Q000201:enzymology*; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology
chemical_list: D016229:Amyloid beta-Peptides; D012433:Ryanodine; D053454:Caspase 12