Impact of Two Neuronal Sigma-1 Receptor Modulators, PRE084 and DMT, on Neurogenesis and Neuroinflammation in an Aβ1–42-Injected, Wild-Type Mouse Model of AD
International Journal of Molecular Sciences February 24, 2022 Emőke Borbély, Viktória Varga, Titanilla Szögi et al. 31 citations
Alzheimer's disease (AD), the most common form of dementia, involves cognitive decline. Two sigma-1 receptor (S1R) agonists, dimethyltryptamine (DMT) and PRE084, were tested in a mouse model of AD induced by amyloid-beta (Aβ). DMT, which also binds strongly to serotonin receptors, reduced neurogenesis, likely due to its mixed receptor activity. In contrast, the highly selective S1R agonist PRE084 increased hippocampal cell proliferation and differentiation. Both DMT and PRE084 significantly reduced astrogliosis (a marker of neuroinflammation) caused by Aβ, but neither affected microglial activation. The findings suggest that selective S1R agonists like PRE084 may be promising therapeutic agents for AD, though further research is needed.