708 Loss of ryanodine receptor calcium release channels in Alzheimer's disease brain

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. Recently, emerging researches on dissociated cells, brains slices, live animal models and patients have demonstrated 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 another alternative pathway, such as the inhibitory effects of NMDA glutamate receptors and the effects of ER-mitochondria connection. However, the therapeutic effects are not consistent. 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.

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Potassium Channels and Internal Calcium Release: Relevance for Memory Storage and Alzheimer’s Disease

Pharmacological Control of Calcium and Potassium Homeostasis - Medical Science Symposia Series ◽

10.1007/978-94-011-0117-2_26 ◽

1995 ◽

pp. 227-235

Author(s):

René Etcheberrigaray ◽

Daniel L. Alkon

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Potassium Channels ◽

Calcium Release ◽

Memory Storage ◽

Internal Calcium

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Divergent Regulation of Ryanodine Receptor 2 Calcium Release Channels by Arrhythmogenic Human Calmodulin Missense Mutants

Circulation Research ◽

10.1161/circresaha.114.303391 ◽

2014 ◽

Vol 114 (7) ◽

pp. 1114-1124 ◽

Cited By ~ 82

Author(s):

Hyun Seok Hwang ◽

Florentin R. Nitu ◽

Yi Yang ◽

Kafa Walweel ◽

Laetitia Pereira ◽

...

Keyword(s):

Ryanodine Receptor ◽

Calcium Release ◽

Calcium Release Channels

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Post-translational remodeling of ryanodine receptor induces calcium leak leading to Alzheimer’s disease-like pathologies and cognitive deficits

Acta Neuropathologica ◽

10.1007/s00401-017-1733-7 ◽

2017 ◽

Vol 134 (5) ◽

pp. 749-767 ◽

Cited By ~ 55

Author(s):

Alain Lacampagne ◽

Xiaoping Liu ◽

Steven Reiken ◽

Renaud Bussiere ◽

Albano C. Meli ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Ryanodine Receptor ◽

Cognitive Deficits

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Altered ryanodine receptor expression in mild cognitive impairment and Alzheimer's disease

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2011.03.011 ◽

2012 ◽

Vol 33 (5) ◽

pp. 1001.e1-1001.e6 ◽

Cited By ~ 48

Author(s):

Angela M. Bruno ◽

Jeff Y. Huang ◽

David A. Bennett ◽

Robert A. Marr ◽

Michelle L. Hastings ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Ryanodine Receptor ◽

Receptor Expression

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Ryanodine receptor Ca2+ release channels: does diversity in form equal diversity in function?

Physiological Reviews ◽

10.1152/physrev.1996.76.4.1027 ◽

1996 ◽

Vol 76 (4) ◽

pp. 1027-1071 ◽

Cited By ~ 282

Author(s):

J. L. Sutko ◽

J. A. Airey

Keyword(s):

Intracellular Calcium ◽

Ryanodine Receptor ◽

Skeletal Muscles ◽

Calcium Release ◽

Cell Types ◽

Calcium Transients ◽

Eukaryotic Cells ◽

Calcium Release Channels ◽

Primary Focus ◽

Fast Twitch

Complexities in calcium signaling in eukaryotic cells require diversity in the proteins involved in generating these signals. In this review, we consider the ryanodine receptor (RyR) family of intracellular calcium release channels. This includes species, tissue, and cellular distributions of the RyRs and mechanisms of activation, deactivation, and inactivation of RyR calcium release events. In addition, as first observed in nonmammalian vertebrate skeletal muscles, it is now clear that more than one RyR isoform is frequently coexpressed within many cell types. How multiple ryanodine receptor release channels are used to generate intracellular calcium transients is unknown. Therefore, a primary focus of this review is why more than one RyR is required for this purpose, particularly in a tissue, such as vertebrate fast-twitch skeletal muscles, where a relatively simple and straightforward change in calcium would appear to be required to elicit contraction. Finally, the roles of the RyR isoforms and the calcium release events they mediate in the development of embryonic skeletal muscle are considered.

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