| First Author | Takata K | Year | 2018 |
| Journal | Neurobiol Aging | Volume | 62 |
| Pages | 197-209 | PubMed ID | 29175709 |
| Mgi Jnum | J:258059 | Mgi Id | MGI:6121184 |
| Doi | 10.1016/j.neurobiolaging.2017.10.021 | Citation | Takata K, et al. (2018) Alpha7 nicotinic acetylcholine receptor-specific agonist DMXBA (GTS-21) attenuates Abeta accumulation through suppression of neuronal gamma-secretase activity and promotion of microglial amyloid-beta phagocytosis and ameliorates cognitive impairment in a mouse model of Alzheimer's disease. Neurobiol Aging 62:197-209 |
| abstractText | We previously demonstrated that stimulation of nicotinic acetylcholine receptors (nAChRs) increases amyloid-beta (Abeta) phagocytosis in rat microglia and is closely associated with the decrease of brain Abeta and amelioration of memory dysfunction in a transgenic mouse model of Alzheimer''s disease (AD). Here, we examined the subtypes of nAChRs involved in these beneficial effects. In primary cultures of rat microglia, the alpha7 nAChR selective agonist 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (DMXBA) promoted Abeta and fluorescent latex bead phagocytosis, whereas selective alpha7 nAChR antagonists suppressed the enhanced Abeta phagocytosis. In a transgenic mouse model of AD, administration of DMXBA attenuated brain Abeta burden and memory dysfunction. Moreover, DMXBA suppressed gamma-secretase activity in solubilized fractions of human neuroblastoma cells and transgenic mouse brain. These results suggested that selective activation of alpha7 nAChRs promoted microglial Abeta phagocytosis and suppressed neuronal gamma-secretase activity to contribute to the attenuation of the brain Abeta burden and cognitive impairment. Thus, we propose neuronal and microglial alpha7 nAChRs as new therapeutic targets in the treatment of AD. |
