Alzheimer’s Disease (AD), a neurodegenerative disorder with high incidence and mortality, is leading its way to the top of the list of the deadliest diseases without an effective disease-modifying drug. Ca2+ dysregulation, specifically abnormal release of Ca2+ via over activated ryanodine receptor (RyR), has been increasingly considered as an alternative upstream mechanism in AD pathology. Consequently, dantrolene, a RyR antagonist and FDA approved drug to treat malignant hyperthermia and chronic muscle spasms, has been shown to ameliorate memory loss in AD transgenic mice. However, the inefficiency of dantrolene to pass the Blood Brain Barrier (BBB) and penetrate the Central Nervous System needs to be resolved, considering its dose-dependent neuroprotection in AD and other neurodegenerative diseases. In this mini-review, we will discuss the current status of dantrolene neuroprotection in AD treatment and a strategy to maximize its beneficial effects, such as intranasal administration of dantrolene.

阿尔茨海默病（AD）是一种发病率和死亡率很高的神经退行性疾病，在没有有效的疾病缓解药物的情况下，它已成为最致命疾病的榜首。 Ca2+ 失调，特别是通过过度激活的兰尼碱受体 (RyR) 异常释放 Ca2+，已越来越多地被认为是 AD 病理学中的另一种上游机制。因此，丹曲林（RyR 拮抗剂和 FDA 批准的治疗恶性高热和慢性肌肉痉挛的药物）已被证明可以改善 AD 转基因小鼠的记忆丧失。然而，考虑到丹曲林在 AD 和其他神经退行性疾病中的剂量依赖性神经保护作用，其通过血脑屏障 (BBB) 和渗透中枢神经系统的效率低下的问题需要解决。在这篇小综述中，我们将讨论丹曲林神经保护在 AD 治疗中的现状以及最大化其有益效果的策略，例如鼻内给药丹曲林。