Title:Approaches to Optimizing Dantrolene Neuroprotection for the Treatment of Alzheimer's Disease
Volume: 17
Issue: 4
Author(s): Matan B. Abou, Liang Sun and Huafeng Wei*
Affiliation:
- Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104,United States
Keywords:
Alzheimer's disease, dantrolene, treatment, intranasal, calcium, blood brain barrier.
Abstract: 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.