Ryanodine receptor dysfunction in human disorders

Alexander Kushnir; Benjamin Wajsberg; Andrew R. Marks

doi:10.1016/j.bbamcr.2018.07.011

Ryanodine receptor dysfunction in human disorders

Alexander Kushnir, Benjamin Wajsberg, Andrew R. Marks

Research output: Contribution to journal › Article › peer-review

72 Scopus citations

Abstract

Regulation of intracellular calcium (Ca ²⁺ ) is critical in all cell types. The ryanodine receptor (RyR), an intracellular Ca ²⁺ release channel located on the sarco/endoplasmic reticulum (SR/ER), releases Ca ²⁺ from intracellular stores to activate critical functions including muscle contraction and neurotransmitter release. Dysfunctional RyR-mediated Ca ²⁺ handling has been implicated in the pathogenesis of inherited and non-inherited conditions including heart failure, cardiac arrhythmias, skeletal myopathies, diabetes, and neurodegenerative diseases. Here we have reviewed the evidence linking human disorders to RyR dysfunction and describe novel approaches to RyR-targeted therapeutics.

Original language	English (US)
Pages (from-to)	1687-1697
Number of pages	11
Journal	Biochimica et Biophysica Acta - Molecular Cell Research
Volume	1865
Issue number	11
DOIs	https://doi.org/10.1016/j.bbamcr.2018.07.011
State	Published - Nov 2018
Externally published	Yes

Keywords

Alzheimer's disease
Arrhythmias
CPVT
Diabetes
Duchenne muscular dystrophy
Heart failure
PTSD
Sarcopenia
Sudden cardiac death

ASJC Scopus subject areas

Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbamcr.2018.07.011

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@article{a005f2eaaac64b39adc0c78a86ff66bb,

title = "Ryanodine receptor dysfunction in human disorders",

abstract = " Regulation of intracellular calcium (Ca 2+ ) is critical in all cell types. The ryanodine receptor (RyR), an intracellular Ca 2+ release channel located on the sarco/endoplasmic reticulum (SR/ER), releases Ca 2+ from intracellular stores to activate critical functions including muscle contraction and neurotransmitter release. Dysfunctional RyR-mediated Ca 2+ handling has been implicated in the pathogenesis of inherited and non-inherited conditions including heart failure, cardiac arrhythmias, skeletal myopathies, diabetes, and neurodegenerative diseases. Here we have reviewed the evidence linking human disorders to RyR dysfunction and describe novel approaches to RyR-targeted therapeutics.",

keywords = "Alzheimer's disease, Arrhythmias, CPVT, Diabetes, Duchenne muscular dystrophy, Heart failure, PTSD, Sarcopenia, Sudden cardiac death",

author = "Alexander Kushnir and Benjamin Wajsberg and Marks, {Andrew R.}",

note = "Funding Information: This work was supported by grants from the NHLBI and NCI to ARM (R01-HL061503, R01-HL140934, R01-AR070194). Columbia University and ARM own stock in ARMGO, Inc. a pharmaceutical company developing compounds targeting RyR. Publisher Copyright: {\textcopyright} 2018 Elsevier B.V.",

year = "2018",

month = nov,

doi = "10.1016/j.bbamcr.2018.07.011",

language = "English (US)",

volume = "1865",

pages = "1687--1697",

journal = "Biochimica et Biophysica Acta - Molecular Cell Research",

issn = "0167-4889",

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number = "11",

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T1 - Ryanodine receptor dysfunction in human disorders

AU - Kushnir, Alexander

AU - Wajsberg, Benjamin

AU - Marks, Andrew R.

N1 - Funding Information: This work was supported by grants from the NHLBI and NCI to ARM (R01-HL061503, R01-HL140934, R01-AR070194). Columbia University and ARM own stock in ARMGO, Inc. a pharmaceutical company developing compounds targeting RyR. Publisher Copyright: © 2018 Elsevier B.V.

PY - 2018/11

Y1 - 2018/11

N2 - Regulation of intracellular calcium (Ca 2+ ) is critical in all cell types. The ryanodine receptor (RyR), an intracellular Ca 2+ release channel located on the sarco/endoplasmic reticulum (SR/ER), releases Ca 2+ from intracellular stores to activate critical functions including muscle contraction and neurotransmitter release. Dysfunctional RyR-mediated Ca 2+ handling has been implicated in the pathogenesis of inherited and non-inherited conditions including heart failure, cardiac arrhythmias, skeletal myopathies, diabetes, and neurodegenerative diseases. Here we have reviewed the evidence linking human disorders to RyR dysfunction and describe novel approaches to RyR-targeted therapeutics.

AB - Regulation of intracellular calcium (Ca 2+ ) is critical in all cell types. The ryanodine receptor (RyR), an intracellular Ca 2+ release channel located on the sarco/endoplasmic reticulum (SR/ER), releases Ca 2+ from intracellular stores to activate critical functions including muscle contraction and neurotransmitter release. Dysfunctional RyR-mediated Ca 2+ handling has been implicated in the pathogenesis of inherited and non-inherited conditions including heart failure, cardiac arrhythmias, skeletal myopathies, diabetes, and neurodegenerative diseases. Here we have reviewed the evidence linking human disorders to RyR dysfunction and describe novel approaches to RyR-targeted therapeutics.

KW - Alzheimer's disease

KW - Arrhythmias

KW - CPVT

KW - Diabetes

KW - Duchenne muscular dystrophy

KW - Heart failure

KW - PTSD

KW - Sarcopenia

KW - Sudden cardiac death

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DO - 10.1016/j.bbamcr.2018.07.011

M3 - Article

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SN - 0167-4889

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JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

IS - 11

ER -

Ryanodine receptor dysfunction in human disorders

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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