RT Journal Article
SR Electronic
T1 Novel botanical therapeutic NB-02 effectively treats Alzheimer’s neuropathophysiology in an APP/PS1 mouse model
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0389-20.2021
DO 10.1523/ENEURO.0389-20.2021
A1 Yee Fun Lee
A1 Lavender Lariviere
A1 Alyssa N. Russ
A1 Sang-Zin Choi
A1 Brian J. Bacskai
A1 Ksenia V. Kastanenka
YR 2021
UL http://www.eneuro.org/content/early/2021/04/27/ENEURO.0389-20.2021.abstract
AB Alzheimer’s disease (AD) is an incurable neurodegenerative disorder and a major cause of dementia. Some of the hallmarks of AD include presence of amyloid plaques in brain parenchyma, calcium dysregulation within individual neurons, and neuroinflammation. A promising therapeutic would reverse or stymie these pathophysiologies in an animal model of AD. We tested the effect of NB-02, previously known as DA-9803, a novel multimodal therapeutic, on amyloid deposition, neuronal calcium regulation and neuroinflammation in 8-10 month old APP/PS1 mice, an animal model of AD. In vivo multiphoton microscopy revealed that 2 month-long administration of NB-02 halted amyloid plaque deposition and cleared amyloid in the cortex. Post-mortem analysis verified NB-02-dependent decrease in plaque deposition in the cortex as well as hippocampus. Furthermore, drug treatment reversed neuronal calcium elevations, thus restoring neuronal function. Finally, NB-02 restored spine density and transformed the morphology of astrocytes as well as microglia to a more phagocytic state, affecting neuroinflammation. NB-02 was effective at reversing AD neuropathophysiology in an animal model. Therefore, in addition to serving as a promising preventative agent, NB-02 holds potential as a treatment for AD in the clinic.Significance StatementNo present cure for Alzheimer’s disease and a great number of clinical trial failures underscores the need for development of therapeutics with multiple mechanisms of action. NB-02 is a multimodal botanical mixture with multiple mechanisms of action. 2-month treatment with NB-02 halts plaque deposition and clears amyloid in cortex as well as hippocampus of APP/PS1 mice. It normalizes neuronal calcium homeostasis, thus restoring neuronal function, and upregulates neuroinflammation. Since NB-02 was effective in slowing pathophysiology in an animal model of amyloidosis, it holds great promise as a therapeutic approach to treat Alzheimer’s disease.