Alzheimer's disease (AD) is a progressive neurodegenerative disorder with loss in memory as one of the cardinal features. 5-N-ethyl carboxamidoadenosine (NECA), an agonist of adenosine-2b receptor, exerts neuroprotective activity against several experimental conditions. Further, NECA activates mitogen-activated protein kinase (MAPK) and also attenuates mitochondrial toxicity in mammalian tissues other than brain. Moreover, there is no report on the role of A2b/MAPK-mediated signaling pathway in Aβ-induced mitochondrial toxicity in the brain of the experimental animals. Therefore, the present study evaluated the neuroprotective activity of NECA with or without MAPK inhibitor against Aβ-induced cognitive deficit and mitochondrial toxicity in the experimental rodents. Further, the effect of NECA with or without MAPK inhibitor was evaluated on Aβ-induced mitochondrial toxicity in the memory-sensitive mice brain regions. Intracerebroventricular (ICV) injection of Aβ 1–42 was injected to healthy male mice through Hamilton syringe via polyethylene tube to induce AD-like behavioral manifestations. NECA attenuated Aβ-induced cognitive impairments in the rodents. In addition, NECA ameliorated Aβ-induced Aβ accumulation and cholinergic dysfunction in the selected memory-sensitive mouse HIP, PFC, and AMY. Further, NECA significantly attenuated Aβ-induced mitochondrial toxicity in terms of decrease in the mitochondrial function, integrity, and bioenergetics in the brain regions of these animals. However, MAPKI diminished the therapeutic effects of NECA on behavioral, biochemical, and molecular observations in AD-like animals. Therefore, it can be speculated that NECA exhibits neuroprotective activity perhaps through MAPK activation in AD-like rodents. Moreover, A2b-mediated MAPK activation could be a promising target in the management of AD.

阿尔茨海默病 (AD) 是一种进行性神经退行性疾病，其主要特征之一是记忆丧失。5-N-乙基羧酰胺腺苷 (NECA) 是腺苷 2b 受体的激动剂，对多种实验条件具有神经保护活性。此外，NECA 激活丝裂原活化蛋白激酶 (MAPK) 并减弱除大脑以外的哺乳动物组织中的线粒体毒性。此外，还没有关于 A2b/MAPK 介导的信号通路在 Aβ 诱导的实验动物脑线粒体毒性中的作用的报道。因此，本研究评估了 NECA 在有或没有 MAPK 抑制剂的情况下对实验啮齿动物中 Aβ 诱导的认知缺陷和线粒体毒性的神经保护活性。更远，在记忆敏感的小鼠大脑区域，评估了 NECA 有或没有 MAPK 抑制剂对 Aβ 诱导的线粒体毒性的影响。通过聚乙烯管通过汉密尔顿注射器向健康雄性小鼠注射 Aβ 1-42 的脑室内 (ICV) 注射剂，以诱导 AD 样行为表现。NECA 减轻了啮齿动物中 Aβ 诱导的认知障碍。此外，NECA 改善了选定的记忆敏感小鼠 HIP、PFC 和 AMY 中 Aβ 诱导的 Aβ 积累和胆碱能功能障碍。此外，NECA 在降低这些动物脑区的线粒体功能、完整性和生物能量学方面显着减弱了 Aβ 诱导的线粒体毒性。然而，MAPKI 减弱了 NECA 对 AD 样动物的行为、生化和分子观察的治疗效果。因此，可以推测 NECA 可能通过 AD 样啮齿动物中的 MAPK 激活表现出神经保护活性。此外，A2b 介导的 MAPK 激活可能是 AD 管理中的一个有希望的目标。