更新于：2024-11-01

核糖核酸酶

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与核糖核酸酶相关的药物

OKG-0303

靶点

核糖核酸酶

作用机制

核糖核酸酶调节剂

在研机构

Okogen, Inc.初创企业

原研机构

Okogen, Inc.初创企业

在研适应症

急性结膜炎

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

Hepatitis B ribozyme gene therapy (Immusol)

靶点

核糖核酸酶

作用机制

核糖核酸酶调节剂 [+1]

在研机构-

原研机构

iTherX Pharmaceuticals, Inc.

在研适应症-

非在研适应症

乙型肝炎

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

Theranase

靶点

核糖核酸酶

作用机制

核糖核酸酶调节剂

在研机构-

原研机构

Sarossa Capital Ltd.

在研适应症-

非在研适应症

淋巴瘤

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与核糖核酸酶相关的临床结果

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100 项与核糖核酸酶相关的转化医学

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0 项与核糖核酸酶相关的专利（医药）

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1,580

项与核糖核酸酶相关的文献（医药）

2024-10-01·Biochimica et Biophysica Acta (BBA) - General Subjects

Keratinocyte and myeloid MCPIP1 have distinct roles in maintaining skin homeostasis

Article

作者: Rumienczyk, Izabela ; Mikula, Michal ; Szukala, Weronika ; Zawada, Roza ; Goryca, Krzysztof ; Lichawska-Cieslar, Agata ; Jura, Jolanta

The skin is a complex organ, and the intricate network between keratinocytes and immune cells is critical for ensuring skin function. Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) is a ribonuclease that functions as a key negative modulator of inflammation. We previously reported that conditional deletion of MCPIP1 in keratinocytes (Mcpip1^EKO) impairs skin integrity in adult mice. A similar phenotype was observed following the depletion of MCPIP1 in the myeloid compartment (Mcpip1^MKO). The aim of this study was to develop a keratinocyte and myeloid double-MCPIP1 knockout mouse model to clarify the specific roles of myeloid and epidermal MCPIP1 in skin biology. Histological analyses indicated that the skin morphology changed after depletion of MCPIP1 in cells of myeloid origin as well as in keratinocytes. The thicknesses of the epidermal and subcutaneous fat layers increased in the mice with a loss of epidermal MCPIP1, whereas the loss of myeloid MCPIP1 had the opposite effect. In addition, both types of mice showed opposite responses to stimulation with 12-O-tetradecanoylphorbol-13-acetate. Transcriptomic profiling of whole-skin lysates revealed some common target transcripts in all the knockout mice. Further analyses revealed that distinct pathways are modulated following the loss of epidermal or myeloid MCPIP1. The skin morphology and inflammatory phenotype of keratinocyte and myeloid double-MCPIP1 knockout mice resembled those of mice with only keratinocyte-specific knockout of MCPIP1. Overall, myeloid and epidermal MCPIP1 play important but distinct roles in the modulation of skin-related processes.

2024-09-24·Proceedings of the National Academy of Sciences

Glial swip-10 controls systemic mitochondrial function, oxidative stress, and neuronal viability via copper ion homeostasis

Article

作者: Gichi, Zayna ; Chang, Christopher J. ; Xiao, Tong ; Gibson, Chelsea L. ; Boerner, Jana ; Carvelli, Lucia ; Kalia, Vrinda ; Fenollar-Ferrer, Cristina ; Blakely, Randy D. ; Rajoo, Andre ; Matier, Carson D. ; Khamoui, Andy V. ; Miller, Gary W. ; Rodriguez, Peter ; Pezacki, Aidan T.

Cuprous copper [Cu(I)] is an essential cofactor for enzymes that support many fundamental cellular functions including mitochondrial respiration and suppression of oxidative stress. Neurons are particularly reliant on mitochondrial production of ATP, with many neurodegenerative diseases, including Parkinson’s disease, associated with diminished mitochondrial function. The gene MBLAC1 encodes a ribonuclease that targets pre-mRNA of replication-dependent histones, proteins recently found in yeast to reduce Cu(II) to Cu(I), and when mutated disrupt ATP production, elevates oxidative stress, and severely impacts cell growth. Whether this process supports neuronal and/or systemic physiology in higher eukaryotes is unknown. Previously, we identified swip-10 , the putative Caenorhabditis elegans ortholog of MBLAC1 , establishing a role for glial swip-10 in limiting dopamine (DA) neuron excitability and sustaining DA neuron viability. Here, we provide evidence from computational modeling that SWIP-10 protein structure mirrors that of MBLAC1 and locates a loss of function coding mutation at a site expected to disrupt histone RNA hydrolysis. Moreover, we find through genetic, biochemical, and pharmacological studies that deletion of swip-10 in worms negatively impacts systemic Cu(I) levels, leading to deficits in mitochondrial respiration and ATP production, increased oxidative stress, and neurodegeneration. These phenotypes can be offset in swip-10 mutants by the Cu(I) enhancing molecule elesclomol and through glial expression of wildtype swip-10 . Together, these studies reveal a glial-expressed pathway that supports systemic mitochondrial function and neuronal health via regulation of Cu(I) homeostasis, a mechanism that may lend itself to therapeutic strategies to treat devastating neurodegenerative diseases.

2024-09-01·Journal of Molecular Biology

RNase R Affects the Level of Fatty Acid Biosynthesis Transcripts Leading to Changes in membrane Fluidity

Article

作者: Arraiano, Cecília Maria ; Pobre, Vânia ; Amblar, Mónica ; Matos, Ana Rita ; Alípio, André Filipe ; Domingues, Susana ; Bárria, Cátia ; Prata, Sara Carrera

Previous studies on RNase R have highlighted significant effects of this ribonuclease in several processes of Streptococcus pneumoniae biology. In this work we show that elimination of RNase R results in overexpression of most of genes encoding the components of type II fatty acid biosynthesis (FASII) cluster. We demonstrate that RNase R is implicated in the turnover of most of transcripts from this pathway, affecting the outcome of the whole FASII cluster, and ultimately leading to changes in the membrane fatty acid composition. Our results show that the membrane of the deleted strain contains higher proportion of unsaturated and long-chained fatty acids than the membrane of the wild type strain. These alterations render the RNase R mutant more prone to membrane lipid peroxidation and are likely the reason for the increased sensitivity of this strain to detergent lysis and to the action of the bacteriocin nisin. Reprogramming of membrane fluidity is an adaptative cell response crucial for bacterial survival in constantly changing environmental conditions. The data presented here is suggestive of a role for RNase R in the composition of S. pneumoniae membrane, with strong impact on pneumococci adaptation to different stress situations.