Matan B. Abou, Liang Sun and Huafeng Wei* Pages 324 - 328 ( 5 )
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.
Alzheimer's disease, dantrolene, treatment, intranasal, calcium, blood brain barrier.
Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104