Novel Botanical Therapeutic NB-02 Effectively Treats Alzheimer's Neuropathophysiology in an APP/PS1 Mouse Model
| Autor: | Yee Fun Lee, Brian J. Bacskai, Alyssa N. Russ, Sang-Zin Choi, Ksenia V. Kastanenka, Lavender Lariviere |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Amyloid
Hippocampus Mice Transgenic Plaque Amyloid Amyloid beta-Protein Precursor Mice astrocyte Alzheimer Disease medicine Dementia Animals Neuroinflammation therapy Amyloid beta-Peptides Microglia business.industry General Neuroscience Amyloidosis General Medicine medicine.disease neuron Disease Models Animal medicine.anatomical_structure Disorders of the Nervous System Neuron business Neuroscience Alzheimer’s disease Research Article: New Research Astrocyte |
| Zdroj: | eNeuro |
| ISSN: | 2373-2822 |
| Popis: | 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 Statement No 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. |
| Databáze: | OpenAIRE |
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