NB-02 Protects Neurons and Astrocytes from Oligomeric Amyloid-β-Mediated Damage

Morgan R Miller; Lavender Lariviere; Guillaume J Pagnier; Sema Aygar; Natalia Wieckiewicz; Masato Maesako; Brian J Bacskai; Ksenia V Kastanenka

doi:10.3233/JAD-231387

NB-02 Protects Neurons and Astrocytes from Oligomeric Amyloid-β-Mediated Damage

J Alzheimers Dis. 2024;99(2):477-483. doi: 10.3233/JAD-231387.

Authors

Morgan R Miller¹, Lavender Lariviere¹, Guillaume J Pagnier¹, Sema Aygar¹, Natalia Wieckiewicz¹, Masato Maesako¹, Brian J Bacskai¹, Ksenia V Kastanenka¹

Affiliation

¹ Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.

PMID: 38669543
DOI: 10.3233/JAD-231387

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease with limited therapeutic strategies. NB-02 is a novel botanical drug that has shown promise as a protective and therapeutic treatment for AD in an APP/PS1 preclinical mouse model. In this paper, we investigate the underlying mechanisms by which NB-02 provides these therapeutic advantages using in vitro neuron-astrocyte co-cultures. Pretreatment with NB-02 prevented pathological calcium elevations in neurons and astrocytes after application of toxic soluble amyloid-β (Aβ) oligomers. NB-02 also prevented cell death associated with the addition of soluble Aβ oligomers suggesting NB-02 is effective at protecting both neurons and astrocytes from Aβ-mediated damage.

Keywords: Alzheimer’s disease; DA-9803; NB-02; amyloid; astrocyte; calcium; neuron; oligomer; therapy.

MeSH terms

Amyloid beta-Peptides* / metabolism
Amyloid beta-Peptides* / toxicity
Animals
Astrocytes* / drug effects
Astrocytes* / metabolism
Calcium / metabolism
Cells, Cultured
Coculture Techniques*
Humans
Mice
Neurons* / drug effects
Neurons* / metabolism
Neurons* / pathology
Neuroprotective Agents* / pharmacology
Peptide Fragments / pharmacology
Peptide Fragments / toxicity