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Neurotherapeutics : the Journal of the... Oct 2018Ryanodine receptor type 1-related myopathies (RYR1-RM) are the most common class of congenital myopathies. Historically, RYR1-RM classification and diagnosis have been... (Review)
Review
Ryanodine receptor type 1-related myopathies (RYR1-RM) are the most common class of congenital myopathies. Historically, RYR1-RM classification and diagnosis have been guided by histopathologic findings on muscle biopsy. Main histological subtypes of RYR1-RM include central core disease, multiminicore disease, core-rod myopathy, centronuclear myopathy, and congenital fiber-type disproportion. A range of RYR1-RM clinical phenotypes has also emerged more recently and includes King Denborough syndrome, RYR1 rhabdomyolysis-myalgia syndrome, atypical periodic paralysis, congenital neuromuscular disease with uniform type 1 fibers, and late-onset axial myopathy. This expansion of the RYR1-RM disease spectrum is due, in part, to implementation of next-generation sequencing methods, which include the entire RYR1 coding sequence rather than being restricted to hotspot regions. These methods enhance diagnostic capabilities, especially given historic limitations of histopathologic and clinical overlap across RYR1-RM. Both dominant and recessive modes of inheritance have been documented, with the latter typically associated with a more severe clinical phenotype. As with all congenital myopathies, no FDA-approved treatments exist to date. Here, we review histopathologic, clinical, imaging, and genetic diagnostic features of the main RYR1-RM subtypes. We also discuss the current state of treatments and focus on disease-modulating (nongenetic) therapeutic strategies under development for RYR1-RM. Finally, perspectives for future approaches to treatment development are broached.
Topics: Animals; Humans; Muscular Diseases; Ryanodine Receptor Calcium Release Channel
PubMed: 30406384
DOI: 10.1007/s13311-018-00677-1 -
Current Pharmaceutical Design 2022The ryanodine receptor (RyR) is one of the primary targets of commercial insecticides. The diamide insecticide family, including flubendiamide, chlorantraniliprole,... (Review)
Review
The ryanodine receptor (RyR) is one of the primary targets of commercial insecticides. The diamide insecticide family, including flubendiamide, chlorantraniliprole, cyantraniliprole, etc., targets insect RyRs and can be used to control a wide range of destructive agricultural pests. The diamide insecticides are highly selective against lepidopteran and coleopteran pests with relatively low toxicity for non-target species, such as mammals, fishes, and beneficial insects. However, recently mutations identified on insect RyRs have emerged and caused resistance in several major agricultural pests throughout different continents. This review paper summarizes the recent findings on the structure and function of insect RyRs as insecticide targets. Specifically, we examine the structures of RyRs from target and non-target species, which reveals the molecular basis for insecticide action and selectivity. We also examine the structural and functional changes of RyR caused by the resistance mutations. Finally, we examine the progress in RyR structure-based insecticide design and discuss how this might help the development of a new generation of green insecticides.
Topics: Animals; Calcium Signaling; Diamide; Humans; Insecticide Resistance; Insecticides; Mammals; Ryanodine Receptor Calcium Release Channel
PubMed: 34477510
DOI: 10.2174/1381612827666210902150224 -
Journal of the American Chemical Society Jul 2020A stereoselective entry to ryanoids is described that culminates in the synthesis of anhydroryanodol and thus the formal total synthesis of ryanodol. The pathway...
A stereoselective entry to ryanoids is described that culminates in the synthesis of anhydroryanodol and thus the formal total synthesis of ryanodol. The pathway described features an annulation reaction conceived to address the uniquely complex and highly oxygenated polycyclic skeleton common to members of this natural product class. It is demonstrated that metallacycle-mediated intramolecular coupling of an alkyne and a 1,3-diketone can proceed with a highly functionalized enyne and with outstanding levels of stereoselection. Furthermore, the first application of this technology in natural product synthesis is demonstrated here. More broadly, the advances described demonstrate the value that programs in natural product total synthesis have in advancing organic chemistry, here through the design and realization of an annulation reaction that accomplishes what previously established reactions do not.
Topics: Biological Products; Cyclization; Molecular Structure; Ryanodine; Stereoisomerism
PubMed: 32609506
DOI: 10.1021/jacs.0c05766 -
Science Signaling Jun 2020In this issue of , Thakore report that the Ca-permeable channel TRPML1 closely associates with ryanodine receptors to induce Ca sparks in native arterial myocytes.... (Review)
Review
In this issue of , Thakore report that the Ca-permeable channel TRPML1 closely associates with ryanodine receptors to induce Ca sparks in native arterial myocytes. Functional studies revealed a key role for TRPML1 channels in regulation of arterial myocyte contractility and blood pressure.
Topics: Calcium; Calcium Signaling; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Ryanodine Receptor Calcium Release Channel
PubMed: 32576679
DOI: 10.1126/scisignal.abc0993 -
Current Pharmaceutical Design 2022
Topics: Acetylcholine; Calcium; Humans; Ryanodine Receptor Calcium Release Channel
PubMed: 35043758
DOI: 10.2174/138161282801211223123314 -
Current Opinion in Pharmacology Feb 2023Myopathies related to variations in the RYR1 gene are genetic diseases for which the therapeutic options are sparse, in part because of the very large size of the gene... (Review)
Review
Myopathies related to variations in the RYR1 gene are genetic diseases for which the therapeutic options are sparse, in part because of the very large size of the gene and protein, and of the distribution of variations all along the sequence. Taking advantage of the progress made in the gene therapy field, different approaches can be applied to the different genetic variations, either at the mRNA level or directly at the DNA level, specifically with the new gene editing tools. Some of those have already been tested in cellulo and/or in vivo, and for the development of the most innovative gene editing technology, inspiration can be sought in other genetic diseases.
Topics: Humans; Ryanodine Receptor Calcium Release Channel; Muscular Diseases; Muscle, Skeletal; Mutation
PubMed: 36529094
DOI: 10.1016/j.coph.2022.102330 -
Anesthesiology Feb 2016
Topics: Calcium Channels; Heat Stress Disorders; Humans; Malignant Hyperthermia; Ryanodine Receptor Calcium Release Channel
PubMed: 26785434
DOI: 10.1097/ALN.0000000000000980 -
Journal of Pediatric Ophthalmology and... May 2018
Review
Topics: DNA; Humans; Malignant Hyperthermia; Motor Neurons; Muscle Contraction; Muscle, Skeletal; Mutation; Ryanodine Receptor Calcium Release Channel
PubMed: 29796677
DOI: 10.3928/01913913-20180409-04 -
Archives of Insect Biochemistry and... Nov 2019Phylogenetic tree of the ryanodine receptor (RyR) family based on maximum likelihood estimation. (Review)
Review
Phylogenetic tree of the ryanodine receptor (RyR) family based on maximum likelihood estimation.
Topics: Alternative Splicing; Animals; Calcium; Homeostasis; Insect Proteins; Insecta; Phylogeny; RNA; Ryanodine Receptor Calcium Release Channel
PubMed: 31218747
DOI: 10.1002/arch.21590