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Dantrolene : From Malignant Hyperthermia to Alzheimer’s Disease

Author(s):

Yun Shi, Yong Wang and Huafeng Wei*   Pages 1 - 9 ( 9 )

Abstract:


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 the disease.

Keywords:

Alzheimer’s disease, dantrolene, therapy, ryanodine receptor, calcium, amyloid

Affiliation:

Department of Anesthesiology and Critical Care, Perelman School of Medicine University of Pennsylvania, 305 John Morgan Building, 3620 Hamilton Walk Philadelphia, PA 19104, Department of Anesthesiology and Critical Care, Perelman School of Medicine University of Pennsylvania, 305 John Morgan Building, 3620 Hamilton Walk Philadelphia, PA 19104, Department of Anesthesiology and Critical Care, Perelman School of Medicine University of Pennsylvania, 305 John Morgan Building, 3620 Hamilton Walk Philadelphia, PA 19104



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