Lithium has been used in the treatment of bipolar disorders for decades,but the exact mechanisms of action remain elusive to this day.Recent evidence suggests that lithium is critically involved in a variety of signal...Lithium has been used in the treatment of bipolar disorders for decades,but the exact mechanisms of action remain elusive to this day.Recent evidence suggests that lithium is critically involved in a variety of signaling pathways affecting apoptosis,inflammation,and neurogenesis,all of which contributing to the complex pathophysiology of various neurological diseases.As a matter of fact,preclinical work reports both acute and longterm neuroprotection in distinct neurological disease models such as Parkinson’s disease,traumatic brain injury,Alzheimer’s disease,and ischemic stroke.Lithium treatment reduces cell injury,decreasesα‑synuclein aggregation and Tau protein phosphorylation,modulates inflammation and even stimulates neuroregeneration under experimental conditions of Parkinson’s disease,traumatic brain injury,and Alzheimer’s disease.The therapeutic impact of lithium under conditions of ischemic stroke was also studied in numerous preclinical in vitro and in vivo studies,giving rise to a randomized double-blind clinical stroke trial.The preclinic data revealed a lithium-induced upregulation of anti-apoptotic proteins such as B-cell lymphoma 2,heat shock protein 70,and activated protein 1,resulting in decreased neuronal cell loss.Lithium,however,does not only yield postischemic neuroprotection but also enhances endogenous neuroregeneration by stimulating neural stem cell proliferation and by regulating distinct signaling pathways such as the RE1-silencing transcription factor.In line with this,lithium treatment has been shown to modulate postischemic cytokine secretion patterns,diminishing microglial activation and stabilizing blood-brain barrier integrity yielding reduced levels of neuroinflammation.The aforementioned observations culminated in a first clinical trial,which revealed an improved motor recovery in patients with cortical stroke after lithium treatment.Beside its well-known psychiatric indications,lithium is thus a promising neuroprotective candidate for the aforementioned neurological diseases.A detailed understanding of the lithium-induced mechanisms,however,is important for prospective clinical trials which may pave the way for a successful benchto-bedside translation in the future.In this review,we will give an overview of lithiuminduced neuroprotective mechanisms under various pathological conditions,with special emphasis on ischemic stroke.展开更多
The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth,migration,and treatment response,thereby influencing tumor progression and therapeutic outcomes.Owing to the prolifer...The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth,migration,and treatment response,thereby influencing tumor progression and therapeutic outcomes.Owing to the proliferation and metastasis of tumors,fibroblast activation protein(FAP)is typically highly expressed in the tumor stroma,whereas it is nearly absent in adult normal tissues and benign lesions,making it an attractive target for precision medicine.Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy.This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization.Within its scope,this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs,combined with insights from structure-activity relationships and clinical studies,providing a valuable perspective for radiopharmaceutical clinical development and application.展开更多
文摘Lithium has been used in the treatment of bipolar disorders for decades,but the exact mechanisms of action remain elusive to this day.Recent evidence suggests that lithium is critically involved in a variety of signaling pathways affecting apoptosis,inflammation,and neurogenesis,all of which contributing to the complex pathophysiology of various neurological diseases.As a matter of fact,preclinical work reports both acute and longterm neuroprotection in distinct neurological disease models such as Parkinson’s disease,traumatic brain injury,Alzheimer’s disease,and ischemic stroke.Lithium treatment reduces cell injury,decreasesα‑synuclein aggregation and Tau protein phosphorylation,modulates inflammation and even stimulates neuroregeneration under experimental conditions of Parkinson’s disease,traumatic brain injury,and Alzheimer’s disease.The therapeutic impact of lithium under conditions of ischemic stroke was also studied in numerous preclinical in vitro and in vivo studies,giving rise to a randomized double-blind clinical stroke trial.The preclinic data revealed a lithium-induced upregulation of anti-apoptotic proteins such as B-cell lymphoma 2,heat shock protein 70,and activated protein 1,resulting in decreased neuronal cell loss.Lithium,however,does not only yield postischemic neuroprotection but also enhances endogenous neuroregeneration by stimulating neural stem cell proliferation and by regulating distinct signaling pathways such as the RE1-silencing transcription factor.In line with this,lithium treatment has been shown to modulate postischemic cytokine secretion patterns,diminishing microglial activation and stabilizing blood-brain barrier integrity yielding reduced levels of neuroinflammation.The aforementioned observations culminated in a first clinical trial,which revealed an improved motor recovery in patients with cortical stroke after lithium treatment.Beside its well-known psychiatric indications,lithium is thus a promising neuroprotective candidate for the aforementioned neurological diseases.A detailed understanding of the lithium-induced mechanisms,however,is important for prospective clinical trials which may pave the way for a successful benchto-bedside translation in the future.In this review,we will give an overview of lithiuminduced neuroprotective mechanisms under various pathological conditions,with special emphasis on ischemic stroke.
基金supported by the National Natural Science Foundation of China(No.82372002)the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences(No.2022-RC350-04)+6 种基金the CAMS Innovation Fund for Medical Sciences(Nos.2024-12M-ZH-009,2023-I2M-2-006,2023-I2M-QJ010,2021-I2M-1-026,and 2021-I2M-3-001,China)the Beijing Nova Program and Beijing Nova Program Interdisciplinary Cooperation Project to Ksupported by the Beijing Natural Science Foundation(Nos.L234044,L248087,L246051 and 7252206,China)the Fundamental Research Funds for the Central Universities(Nos.3332023044,3332023151,China)the China Postdoctoral Science Foundation(No.2025M773592)the China National Nuclear Corporation Young Talent Program,the special project of“Technological Innovation”project of CNNC Medical Industry Co.Ltd(ZHYLYB2021005)Medical+X Innovation Team of the Discipline Construction Enhancement Project,the Second Affiliated Hospital of Soochow University(XKTJ-TD202410).
文摘The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth,migration,and treatment response,thereby influencing tumor progression and therapeutic outcomes.Owing to the proliferation and metastasis of tumors,fibroblast activation protein(FAP)is typically highly expressed in the tumor stroma,whereas it is nearly absent in adult normal tissues and benign lesions,making it an attractive target for precision medicine.Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy.This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization.Within its scope,this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs,combined with insights from structure-activity relationships and clinical studies,providing a valuable perspective for radiopharmaceutical clinical development and application.
