Neuroprotective Effects of Ferruginol, Jatrophone, and Junicedric Acid Against Amyloid-β Injury in Hippocampal Neurons
Inestrosa, Nibaldo C.
- 1
- 2Pontificia Universidad Catolica de Chile
- 3Universidad de Talca
- 4
Journal
Journal of Alzheimer'S Disease
ISSN
1387-2877
1875-8908
Open Access
closed
Volume
63
Start page
705
End page
723
Soluble amyloid-beta (A beta) oligomers have been recognized as early neurotoxic intermediates with a key role in the synaptic dysfunction observed in Alzheimer's disease (AD). A beta oligomers block hippocampal long-term potentiation (LTP) and impair rodent spatial memory. Additionally, the presence of A beta oligomers is associated with imbalanced intracellular calcium levels and apoptosis in neurons. In this context, we evaluated the effects of three diterpenes (ferruginol, jatrophone, and junicedric acid) that are found in medicinal plants and have several forms of biological activity. The intracellular calcium levels in hippocampal neurons increased in the presence of ferruginol, jatrophone, and junicedric acid, a result that was consistent with the observed increase in CA1 synaptic transmission in mouse hippocampal slices. Additionally, assays using A beta peptide demonstrated that diterpenes, particularly ferruginol, restore LTP and reduce apoptosis. Recovery of the A beta oligomer-induced loss of the synaptic proteins PSD-95, synapsin, VGlut, and NMDA receptor subunit 2A was observed in mouse hippocampal slices treated with junicedric acid. This cascade of events may be associated with the regulation of kinases, e.g., protein kinase C (PKC) and calcium/calmodulin- dependent protein kinase II (CaMKII), in addition to the activation of the canonical Wnt signaling pathway and could thus provide protection against A beta oligomers, which trigger synaptic dysfunction. Our results suggest a potential neuroprotective role for diterpenes against the A beta oligomers-induced neurodegenerative alterations, which make them interesting molecules to be further studied in the context of AD.