Pamiparib is a potent and selective oral poly(adenosine diphosphate(ADP)-ribose)-polymerase(PARP)1/2inhibitor(PARPi).Pamiparib has good bioavailability and shows greater cytotoxic potency and similar DNA-trapping capa...Pamiparib is a potent and selective oral poly(adenosine diphosphate(ADP)-ribose)-polymerase(PARP)1/2inhibitor(PARPi).Pamiparib has good bioavailability and shows greater cytotoxic potency and similar DNA-trapping capacity compared to olaparib.It is not affected by adenosine triphosphate(ATP)-binding cassette transporters.展开更多
Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that jimit the pathological changes and improve the behavioral outcome have been w...Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that jimit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially per- oxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly（ADP-ribose） polymerase （PARP） upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neu- ronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the in- volvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.展开更多
Poly(ADP-ribose)(PAR),a polymer of ADP-ribose,is synthesized by PAR po-lymerase and is crucial for the survival of cancer cells due to its vital functions in DNA repair and post-translational modifications.Beyond its ...Poly(ADP-ribose)(PAR),a polymer of ADP-ribose,is synthesized by PAR po-lymerase and is crucial for the survival of cancer cells due to its vital functions in DNA repair and post-translational modifications.Beyond its supportive role,PAR also triggers cancer cell death by excessive accumulation of PAR leading to an energy crisis and parthanatos.This phenomenon underscores the potential of targeting PAR regulation as a novel anticancer strategy,and the rationale would present an engaging topic in the field of anticancer research.Therefore,this editorial provides an overview of the mechanisms determining cancer cell fate,emphasizing the central role of PAR.It further introduces promising methods for modulating PAR concentrations that may pave the way for innovative anticancer therapies.展开更多
系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种以I型干扰素(type I interferon,IFN-I)通路异常激活和病理性自身抗体大量生成为特征的自身免疫性疾病。近年来研究发现,ADP-核糖基化修饰通过调控T淋巴细胞分化、B细胞抗体分...系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种以I型干扰素(type I interferon,IFN-I)通路异常激活和病理性自身抗体大量生成为特征的自身免疫性疾病。近年来研究发现,ADP-核糖基化修饰通过调控T淋巴细胞分化、B细胞抗体分泌等免疫过程。多聚ADP-核糖聚合酶家族成员14[poly(adp-ribose)polymerase family member 14,PARP14]作为多功能ADP-核糖基化转移酶,不仅能通过单ADP-核糖基化修饰动态修饰靶蛋白、DNA、RNA等生物大分子,还在DNA损伤修复、炎症调控及免疫稳态维持中发挥关键作用。本文系统综述PARP14通过表观遗传和免疫调节影响SLE发生发展的分子机制。展开更多
基金supported in part by funding from BeiGene,Ltd.,USA(Grant No.:KPR081)with additional support from the Alessandra Bono Foundation,Italy.
文摘Pamiparib is a potent and selective oral poly(adenosine diphosphate(ADP)-ribose)-polymerase(PARP)1/2inhibitor(PARPi).Pamiparib has good bioavailability and shows greater cytotoxic potency and similar DNA-trapping capacity compared to olaparib.It is not affected by adenosine triphosphate(ATP)-binding cassette transporters.
基金Department of Biotechnology Govt of India,for their financial support to Dr.Ashutosh Kumar via grant BT/527/NE/TBP/2013the financial support from Department of Pharmaceuticals,Ministry of Chemical and Fertilizers and NIPER Hyderabad for their support
文摘Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that jimit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially per- oxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly（ADP-ribose） polymerase （PARP） upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neu- ronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the in- volvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.
文摘Poly(ADP-ribose)(PAR),a polymer of ADP-ribose,is synthesized by PAR po-lymerase and is crucial for the survival of cancer cells due to its vital functions in DNA repair and post-translational modifications.Beyond its supportive role,PAR also triggers cancer cell death by excessive accumulation of PAR leading to an energy crisis and parthanatos.This phenomenon underscores the potential of targeting PAR regulation as a novel anticancer strategy,and the rationale would present an engaging topic in the field of anticancer research.Therefore,this editorial provides an overview of the mechanisms determining cancer cell fate,emphasizing the central role of PAR.It further introduces promising methods for modulating PAR concentrations that may pave the way for innovative anticancer therapies.
基金This work was partly supported by research grants No. 81072703 （to Dr. Yu） from the National Natural Science Foundation, Beijing, P.R. China, a research grant No. 10411951700 （to Dr. Zhang） from Science and Technology Commission of Shanghai Municipality, Shanghai, P.R. China.The authors confirm that there are no conflicts of interests.
文摘系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种以I型干扰素(type I interferon,IFN-I)通路异常激活和病理性自身抗体大量生成为特征的自身免疫性疾病。近年来研究发现,ADP-核糖基化修饰通过调控T淋巴细胞分化、B细胞抗体分泌等免疫过程。多聚ADP-核糖聚合酶家族成员14[poly(adp-ribose)polymerase family member 14,PARP14]作为多功能ADP-核糖基化转移酶,不仅能通过单ADP-核糖基化修饰动态修饰靶蛋白、DNA、RNA等生物大分子,还在DNA损伤修复、炎症调控及免疫稳态维持中发挥关键作用。本文系统综述PARP14通过表观遗传和免疫调节影响SLE发生发展的分子机制。
