神经炎症
兴奋剂
神经病理学
医学
转基因小鼠
药理学
Sigma-1受体
内科学
受体
内分泌学
神经科学
疾病
化学
转基因
心理学
基因
生物化学
作者
Hélène Hall,M. Florencia Iulita,Palma Gubert,Lisi Flores Aguilar,Adriana Ducatenzeiler,Abraham Fisher,A. Claudio Cuello
标识
DOI:10.1016/j.jalz.2017.11.009
摘要
AF710B (aka ANAVEX 3-71) is a novel selective allosteric M1 muscarinic and sigma-1 receptor agonist. In 3×Tg-AD mice, AF710B attenuates cognitive deficits and decreases Alzheimer-like hallmarks. We now report on the long-lasting disease-modifying properties of AF710B in McGill-R-Thy1-APP transgenic (Tg) rats.Chronic treatment with AF710B (10 μg/kg) was initiated in postplaque 13-month-old Tg rats. Drug or vehicle was administered orally daily for 4.5 months and interrupted 5 weeks before behavioral testing.AF710B long-term treatment reverted the cognitive deficits associated with advanced Alzheimer-like amyloid neuropathology in Tg rats. These effects were accompanied by reductions in amyloid pathology and markers of neuroinflammation and increases in amyloid cerebrospinal fluid clearance and levels of a synaptic marker. Importantly, these effects were maintained following a 5-week interruption of the treatment.With M1/sigma-1 activity and long-lasting disease-modifying properties at low dose, AF710B is a promising novel therapeutic agent for treating Alzheimer's disease.
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