Novel botanical drug DA-9803 prevents deficits in Alzheimer's mouse models.

Abstract

BACKGROUND:

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by deposition of amyloid plaques and disruption of neural circuitry, leading to cognitive decline. Animal models of AD deposit senile plaques and exhibit structural and functional deficits in neurons and neural networks. An effective treatment would prevent or restore these deficits, including calcium dyshomeostasis observed with in-vivo imaging.

METHODS:

We examined the effects of DA-9803, a multimodal botanical drug, in 5XFAD and APP/PS1 transgenic mice which underwent daily oral treatment with 30 or 100 mg/kg DA-9803 or vehicle alone. Behavioral testing and longitudinal imaging of amyloid deposits and intracellular calcium in neurons with multiphoton microscopy was performed.

RESULTS:

Chronic administration of DA-9803 restored behavioral deficits in 5XFAD mice and reduced amyloid-β levels. DA-9803 also prevented progressive amyloid plaque deposition in APP/PS1 mice. Elevated calcium, detected in a subset of neurons before the treatment, was restored and served as a functional indicator of treatment efficacy in addition to the behavioral readout. In contrast, mice treated with vehicle alone continued to progressively accumulate amyloid plaques and calcium overload.

CONCLUSIONS:

In summary, treatment with DA-9803 prevented structural and functional outcome measures in mouse models of AD. Thus, DA-9803 shows promise as a novel therapeutic approach for Alzheimer's disease.

• Authors: Guillaume J Pagnier, Ksenia V Kastanenka, Miwon Sohn, Sangzin Choi, Song-Hyen Choi, HyeYeon Soh, Brian J Bacskai
• Journal: Alzheimer's research & therapy (Alzheimers Res Ther) Vol. 10 Issue 1 Pg. 11 (01 29 2018) ISSN: 1758-9193 [Electronic] England
• PMID: 29378621 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• APP protein, human
• Amyloid beta-Protein Precursor
• Neuroprotective Agents
• Nootropic Agents
• PSEN1 protein, human
• Presenilin-1
• Calcium

Topics

• Administration, Oral
• Alzheimer Disease (drug therapy, metabolism, pathology)
• Amyloid beta-Protein Precursor (genetics, metabolism)
• Animals
• Brain (drug effects, metabolism, pathology)
• Calcium (metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Humans
• Learning (drug effects)
• Longitudinal Studies
• Male
• Mice, Transgenic
• Neuroprotective Agents (pharmacology)
• Nootropic Agents (pharmacology)
• Phytotherapy
• Plaque, Amyloid (drug therapy, metabolism, pathology)
• Presenilin-1 (genetics, metabolism)
• Random Allocation