Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder in which the amyloid-β (Aβ) oligomers are a key factor in synaptic impairment and in spatial memory decline associated with neuronal dysfunction. This impairment includes synaptic failure associated with the loss of synaptic proteins that contribute to AD progression. Interestingly, the use of natural compounds is an emergent conceptual strategy in the search for drugs with therapeutic potentials for treating neurodegenerative disorders. In the present study, we report that andrographolide (ANDRO), which is a labdane diterpene extracted from Andrographis paniculata, increases slope of field excitatory postsynaptic potentials (fEPSP) in the CA1 region of hippocampal slices and inhibits long-term depression (LTD), protecting the long-term potentiation (LTP) against the damage induced by Aβ oligomers in vitro, most likely by inhibiting glycogen synthase kinase-3β (GSK-3β). Additionally, ANDRO prevents changes in neuropathology in two different age groups (7- and 12-month-old mice) of an AβPPswe/PS-1 Alzheimer’s model. ANDRO reduces the Aβ levels, changing the ontogeny of amyloid plaques in hippocampi and cortices in 7-month-old mice, and reduces tau phosphorylation around the Aβ oligomeric species in both age groups. Additionally, we observed that ANDRO recovers spatial memory functions that correlate with protecting synaptic plasticity and synaptic proteins in two different age groups. Our results suggest that ANDRO could be used in a potential preventive therapy during AD progression.Electronic supplementary materialThe online version of this article (doi:10.1186/1750-1326-9-61) contains supplementary material, which is available to authorized users.
Highlights
Alzheimer’s disease (AD), which is the most common cause of dementia, currently has no known cure
ANDRO decreases amyloid β-peptide (Aβ) depositions in young AβPPswe/PS-1 mice Previous studies have suggested that amyloid levels in AD patients and mouse models are related to cognitive impairment [22]; the effects of Aβ oligomers are thought to be the cause of synaptic function impairment in the postsynaptic region [23,24,25]
The aggregate size distribution, which is presented as a cumulative frequency plot, demonstrates that AβPPswe/PS-1 mice treated with ANDRO shifted their plaque size distribution toward a smaller plaque size from cortex (Figure 1c)
Summary
Alzheimer’s disease (AD), which is the most common cause of dementia, currently has no known cure. The role of ANDRO in neurodegenerative diseases, such as AD, has not been investigated
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
