Background & Objective: Dantrolene, a ryanodine receptor antagonist, is primarily known
as the only clinically acceptable and effective treatment for malignant hyperthermia (MH). Inhibition
of ryanodine receptor (RyR) by dantrolene decreases the abnormal calcium release from the sarcoplasmic
reticulum (SR) or endoplasmic reticulum (ER), where RyR is located on. Recently, emerging
researches on dissociated cells, brains slices, live animal models and patients demonstrate that altered
RyR expression and function can also play a vital role in the pathogenesis of Alzheimer’s disease (AD).
Therefore, dantrolene is now widely studied as a novel treatment for AD, targeting the blockade of RyR
channels or other alternative pathways, such as the inhibitory effects of NMDA glutamate receptors and
the effects of ER-mitochondria connection. However, the therapeutic effects are not consistent.
Conclusion: In this review, we focus on the relationship between the altered RyR expression and function
and the pathogenesis of AD, and the potential application of dantrolene as a novel treatment for