Edonerpic maleate (T-817 maleate) is a neurotrophic agent which can inhibit amyloid-β peptides (Aβ).

β-Amyloid:

Treatment with Edonerpic maleate (T-817MA) effectively preserves cortical neurons against Aβ(1-42) damage. By pre-treating for twenty-four hours and maintaining continuous exposure, Edonerpic maleate safeguards neurons from oxidative stress-induced death and nearly completely inhibits GSH reduction at both 0.1 and 1 μM concentrations. Furthermore, hippocampal slices exposed to 1 μM of Edonerpic maleate exhibit a significant increase in the generation and elongation of neurites compared to untreated controls, with notable enhancements in neurite length observed at concentrations of 0.1 and 1 μM.

The post hoc analysis revealed that the average density of PSA-positive cells was significantly higher in both the vehicle and the Aβ infusion plus high-dose Edonerpic maleate (T-817MA) groups compared to the Aβ infusion control group (P<0.01). These findings suggest that the vehicle and Aβ infusion combined with high-dose Edonerpic maleate groups not only demonstrate enhanced learning capabilities in the place learning task (PLT) but also show increased neurogenesis. However, the administration of Edonerpic maleate and donepezil did not lead to a significant change in the average density of normal granule cells, indicating no notable differences in granule cell density between the Aβ infusion control group, and the groups treated with Aβ infusion plus high-dose Edonerpic maleate, Aβ infusion plus low-dose Edonerpic maleate, and Aβ infusion plus donepezil.

A cortical neuron/glia coculture is prepared. Edonerpic maleate (T-817MA) is added to the cocultures at concentrations of 0 (control), 0.01, 0.1, and 1 μM, and the cells are subsequently incubated for 5 min or 24 h. H2O2 is then added to the coculture at a concentration of 100 μM, and the cells are incubated for another 24 h. For the normal group, the preparations are maintained in the medium with neither Edonerpic maleate nor H2O2. Neuronal cell viability is quantified by measuring the Monoclonal anti-microtubule-associated protein 2 (MAP2) immunoreactivity

Edonerpic maleate (T-817MA) (high-dose: 8.4 mg/kg and low-dose: 0.84 mg/kg) and donepezil (0.5 mg/kg) are dissolved in distilled water in a volume of 5 mL/kg.Wistar rats (7 weeks, n=47) are used in this study. All rats are given food and water ad libitum in a clear cage and handled on three consecutive days before start of the experiments. The housing area is provided a temperature-controlled environment under a 12/12 h light cycle. These rats are divided into five groups: vehicle (n=11), Aβ infusion control (n=10), Aβ infusion+high-dose Edonerpic maleate (T-817MA) (8.4 mg/kg) (n=11), Aβ infusion+low-dose Edonerpic maleate (0.84 mg/kg) (n=9) and Aβ infusion+donepezil (0.5 mg/kg) (n=7)

DMSO: 155 mg/mL (380.39 mM), Sonication is recommended.