Wnt Signaling Prevents the Aβ Oligomer-Induced Mitochondrial Permeability Transition Pore Opening Preserving Mitochondrial Structure in Hippocampal Neurons

摘要: Alzheimer’s disease (AD) is a neurodegenerative disorder mainly known for synaptic impairment and neuronal cell loss, affecting memory processes. Beside these damages, mitochondria have been implicated in the pathogenesis of AD through induction mitochondrial permeability transition pore (mPTP). The mPTP non-selective that formed under apoptotic conditions, disturbing structure thus, viability. In AD, Aβ oligomers (Aβos) favor opening pore, activating mitochondria-dependent death cascades. Wnt signaling activated ligand Wnt3a has described as neuroprotective pathway against amyloid-β (Aβ) peptide toxicity AD. However, mechanisms by which prevents Aβos-induced are unclear. We proposed here to study whether protects neurons earlier than late damages progression disease, preservation inhibition. To specific events related permeabilization we performed live-cell imaging from primary rat hippocampal neurons, electron microscopy analyze morphology structure. report an cascade leads death. This involves (a) opening, (b) swelling, (c) membrane potential loss (d) cytochrome c release, thus leading Furthermore, our results suggest activation two possible mechanisms, involve inhibition GSK-3β and/or modulation hexokinase II levels activity. suggests new approach treatment perspective, will also open lines field neuroprotection.