SOD/Catalase mimics for age-related learning impairment

描述改编自申请人的摘要）：衰老是伴随着一个缓慢的 认知功能下降，现在称为轻度认知障碍 (MCI)以及氧化蛋白质和脂质的积累， 氧化应激Eukarion发现了一类新的锰络合物 其显示超氧化物歧化酶（SOD）和过氧化氢酶活性。这些 SOD/过氧化氢酶模拟物在几种人类疾病模型中显示出有效性 其中涉及氧化应激。特别是，EUK-134已被 在啮齿类动物中风模型和红藻氨酸中发现具有高度保护作用。 酸诱导的神经元损伤。它还减少了氧化应激， 在ALS小鼠模型中的存活率。本项目旨在测试 EUK-134和另一种类似物对年龄相关的氧化应激的功效， 小鼠的学习和记忆障碍。八个月大的老鼠将被治疗 用EUK-134和另一种类似物治疗3个月他们将接受测试， 获得和保留2个不同的任务，回避学习范式， 和恐惧调节模式。将测量氧化应激标志物 在不同的大脑结构中，并与行为测量相关。是我们 我希望这些研究的结果能够证明 EUK分子对治疗MCI患者的价值。 拟议商业应用：不可用

DESCRIPTION Adapted from applicant's abstract): Aging is accompanied by a slow decline in cognitive function, now referred to as mild cognitive impairment (MCI), and by accumulation of oxidized proteins and lipids as a result of oxidative stress. Eukarion has discovered a new class of manganese complexes that display both superoxide dismutase (SOD) and catalase activities. These SOD/catalase mimetics have shown efficacy in several models of human diseases in which oxidative stress has been implicated. In particular, EUK-134 has been found to be highly protective in a rodent model for stroke and in kainic acid-induced neuronal damage. It also reduced oxidative stress and prolonged survival in a mouse model for ALS. The present project is directed at testing the efficacy of EUK-134 and another analog on age-related oxidative stress and learning and memory impairment in mice. Eight month-old mice will be treated with EUK-134 and another analog for 3 months. They will be tested for acquisition and retention of 2 different tasks, an avoidance learning paradigm, and a fear-conditioning paradigm. Markers of oxidative stress will be measured in various brain structures and correlated with behavioral measures. It is our hope that results from these studies will demonstrate the potential therapeutic values of EUK molecules for treating patients with MCI. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE