copper chelator induced efficient episodic memory recovery in a non-transgenic alzheimer’s mouse model铜螯合剂诱发有效的情景记忆复苏非转基因阿尔茨海默病小鼠模型.pdfVIP

Copper Chelator Induced Efficient Episodic Memory Recovery in a Non-Transgenic Alzheimer’s Mouse Model 1 ´ ´ ´ 3 ´ ` 1,2 ` 1,2 1,2 . Johnatan Ceccom , Frederic Cosledan , Helene Halley , Bernard Frances , Jean Michel Lassalle * , Bernard Meunier3,4*. ´ 1 Universite de Toulouse, UPS, Centre de Recherches sur la Cognition Animale, Toulouse, France, 2 CNRS, Centre de Recherches sur la Cognition Animale, Toulouse, France, 3 Palumed, Castanet-Tolosan, France, 4 Laboratoire de Chimie de Coordination du CNRS, Toulouse, France Abstract Alzheimer’s disease (AD) is a neurodegenerative syndrom involving many different biological parameters, including the accumulation of copper metal ions in Ab amyloid peptides due to a perturbation of copper circulation and homeostasis within the brain. Copper-containing amyloids activated by endogenous reductants are able to generate an oxidative stress that is involved in the toxicity of abnormal amyloids and contribute to the progressive loss of neurons in AD. Since only few drugs are currently available for the treatment of AD, we decided to design small molecules able to interact with copper and we evaluated these drug-candidates with non-transgenic mice, since AD is mainly an aging disease, not related to genetic disorders. We created a memory deficit mouse model by a single icv injection of Ab1–42 peptide, in order to mimic the early stage of the disease and the key role of amyloid oligomers in AD. No memory deficit was observed in the control mice with the antisense Ab42-1 peptide. Here we report the capacity of a new copper-specific chelating agent, a bis-8-aminoquinoline PA1637, to f