A Novel Neurotrophic Agent, T-817MA [1-{3-[2-(1-Benzothiophen-5-yl) Ethoxy] Propyl}-3-azetidinol Maleate], Attenuates Amyloid-β-Induced Neurotoxicity and Promotes Neurite Outgrowth in Rat Cultured Central Nervous System Neurons

Abstract

Progressive neuronal loss in Alzheimer's disease (AD) is considered to be a consequence of the neurotoxic properties of amyloid-␤ peptides (A␤). T-817MA (1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl}-3-azetidinol maleate) was screened as a candidate therapeutic agent for the treatment of AD based on its neuroprotective potency against A␤-induced neurotoxicity and its effect of enhancing axonal regeneration in the sciatic nerve axotomy model. The neuroprotective effect of T-817MA against A␤(1-42) or oxidative stress-induced neurotoxicity was assessed using a coculture of rat cortical neurons with glia.

Strategies for the Inhibition of Protein Aggregation in Human Diseases

“…[266] As a final remark, neuroprotective agents have also been developed. 1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate (T-817MA) [267] is now in phase IIa trials in patients with mild to moderate AD.…”

T-817MA, a novel neurotrophic compound, ameliorates phencyclidine-induced disruption of sensorimotor gating

“…In vitro, T-817MA exerts neuroprotective actions against neurotoxicity induced by amyloid-β peptide or hydrogen peroxide in the coculture of cortical neurons with glia cells. It also promotes neurite outgrowth both in the hippocampal slice and cortical reaggregation culture from rats (Hirata et al 2005). Fukushima et al (2006) reported that T-817MA ameliorates sodium nitroprusside-induced mitochondrial dysfunction in rat cortical neurons.…”

“…T-817MA (1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl} azetidin-3-ol maleate) is a novel compound, and is suggested to be useful for ameliorating symptoms of neurodegenerative disorders, such as Alzheimer's disease (Hirata et al 2005;Nguyen et al 2007). In vitro, T-817MA exerts neuroprotective actions against neurotoxicity induced by amyloid-β peptide or hydrogen peroxide in the coculture of cortical neurons with glia cells.…”

Oral Administration of Pharmacologically Active Substances to Squid: A Methodological Description

“…A second group of squid was fed twice (at a 24-h interval) 0.25 ml of 36.8 mmol l Ϫ1 T-817. T-817 is a neuroprotective compound developed by Toyama Chemical of Japan (Hirata et al, 2005).…”