Bryostatin-1 protects against amyloid- beta (Aβ) oligomer-induced neurotoxicity by activating autophagy
DOI:
https://doi.org/10.1590/Keywords:
Aβ oligomer toxicity, Bryostatin-1, Autophagy influxAbstract
The expression of PKCε, a member of the protein kinase C family, has been found to be decreased in the frontal cortex of patients with Alzheimer’s disease (AD). Bryostatin-1 is a PKCε activator and has shown benefits in AD animal models. However, how Bryo-1 protects neuronal activity and synaptic function in AD pathology is still unknown. In the present study, we first established an Aβ toxicity cell model by administering Aβ 25-35 oligomers to cultured primary hippocampal neurons. We then evaluated the protective effect of Bryo-1 on this model by administering Bryo-1 together with Aβ oligomers. Finally, we investigated the autophagic influx of primary hippocampal neurons in the presence of Aβ oligomers and Bryo-1. Imaging and electrophysiology recordings showed that Bryo-1 protected synaptic dynamics and functions against the neurotoxicity of Aβ oligomers. Furthermore, Bryo-1 was also found to rescue autophagy influx that was impaired by Aβ oligomer treatment. This discovery may explain the beneficial effects of Bryo-1 in AD animal models. In summary, we discovered a novel mechanism by which Bryo-1 protects neurons against Aβ oligomer-induced neurotoxicity. Our results may support the concept of developing PKCε activators as therapeutics for AD.
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