Spinal cord injury is a severe neurological condition with limited neuronal regeneration and functional recovery.Currently,no effective treatments exist to improve spinal cord injury prognosis.Neuronal guidance protei...Spinal cord injury is a severe neurological condition with limited neuronal regeneration and functional recovery.Currently,no effective treatments exist to improve spinal cord injury prognosis.Neuronal guidance proteins are a diverse group of molecules that play crucial roles in axon and dendrite growth during nervous system development.Increasing evidence highlights their regulatory functions in spinal cord injury.This review provides a brief overview of the modulation patterns of key neuronal guidance proteins in neuronal axon growth during nervous system formation and subsequently focuses on their roles in neuronal regeneration and functional recovery following spinal cord injury.Neuronal guidance proteins include,but are not limited to,semaphorins and their receptors,plexins;netrins and their receptors,deleted in colorectal cancer and UNC5;Eph receptors and their ligands,ephrins;Slit and its receptor,Robo;repulsive guidance molecules and their receptor,neogenin;Wnt proteins and their receptor,Frizzled;and protocadherins.Localized Netrin-1 at the injury site inhibits motor axon regeneration after adult spinal cord injury while promoting oligodendrocyte growth.Slit2 enhances synapse formation in the injured spinal cord of rats.EphA7 regulates acute apoptosis in the early pathophysiological stages of spinal cord injury,while ephrinA1 plays a role in the nervous system’s injury response,with its reduced expression leading to impaired motor function in rats.EphA3 is upregulated following spinal cord injury,promoting an inhibitory environment for axonal regeneration.After spinal cord injury,bidirectional activation of ephrinB2 and EphB2 in astrocytes and fibroblasts results in the formation of a dense astrocyte-meningeal fibroblast scar.EphB1/ephrinB1 signaling mediates pain processing in spinal cord injury by regulating calpain-1 and caspase-3 in neurons.EphB3 expression increases in white matter after spinal cord injury,further inhibiting axon regeneration.Sema3A,expressed by neurons and fibroblasts in the scar surrounding the injury,inhibits motor neuron and sensory nerve growth after spinal cord injury.Sema4D suppresses neuronal axon myelination and axon regeneration,while its inhibition significantly enhances axon regeneration and motor recovery.Sema7A is involved in glial scar formation and may influence serotonin channel remodeling,thereby affecting motor coordination.Given these findings,the local or systemic application of neuronal guidance proteins represents a promising avenue for spinal cord injury treatment.展开更多
信号素(Semaphorin)作为一组多功能的蛋白质,占据神经系统功能发育的关键,包括对调节突触形成和神经元的生长的同时,还参与调控细胞周期、影响细胞形态的转变,以及在肿瘤学中,它们能够影响肿瘤细胞的生长、侵袭和转移,以及在免疫反应中...信号素(Semaphorin)作为一组多功能的蛋白质,占据神经系统功能发育的关键,包括对调节突触形成和神经元的生长的同时,还参与调控细胞周期、影响细胞形态的转变,以及在肿瘤学中,它们能够影响肿瘤细胞的生长、侵袭和转移,以及在免疫反应中发挥作用。信号素(Semaphorin, SEMA)是一类分泌型、膜结合型或糖磷脂酰肌醇锚定的糖蛋白,与神经发育、轴突引导、骨分化、心血管系统以及癌症等相关。Sema3F (Semaphorin 3F)是信号素家族轴突引导分子的一种分泌型,参与神经元的发育。Sema3F及其受体神经纤毛蛋白-2在胚胎小鼠大脑区域(包括嗅球、海马体和大脑皮层)中以互斥方式表达。Sema3F作用在神经元上,可引起下游因子的改变,包括CREBBP、CREB、VEGF等,能够下调P53表达、影响GABA能系统、下调RacGTP水平、促进CRMP2磷酸化等。本文通过综述的方法,对Sema3F在神经元下游因子进行叙述,为研究Sema3F在神经元中的功能提供帮助。Semaphorin, as a group of multifunctional proteins, plays a crucial role in the functional development of the nervous system. It not only regulates synapse formation and the growth of neurons but also participates in the regulation of the cell cycle, influences the transformation of cell morphology. Moreover, in oncology, it can affect the growth, invasion and metastasis of tumor cells and also plays a role in immune responses. Semaphorin (SEMA) is a type of secreted, membrane-bound or glycosylphosphatidylinositol-anchored glycoprotein, which is related to neural development, axon guidance, bone differentiation, the cardiovascular system and cancer, etc. Sema3F, a secreted form of the axon guidance molecules in the Semaphorin family, is involved in the development of neurons. Sema3F and its receptor neuropilin-2 are expressed in a mutually exclusive manner in the brain regions (including the olfactory bulb, hippocampus and cerebral cortex) of embryonic mice. When Sema3F acts on neurons, it can cause changes in downstream factors, including CREBBP, CREB, VEGF, etc. It can downregulate the expression of P53, affect the GABAergic system, downregulate the level of RacGTP and promote the phosphorylation of CRMP2, etc. Through the method of review, this article describes the downstream factors of Sema3F in neurons, aiming to provide assistance for the research on the functions of Sema3F in neurons.展开更多
Osteoarthritis(OA)is a degenerative joint disease accompanied with the loss of cartilage and consequent nociceptive symptoms.Normal articular cartilage maintains at aneural state.Neuron guidance factor Semaphorin 3A(S...Osteoarthritis(OA)is a degenerative joint disease accompanied with the loss of cartilage and consequent nociceptive symptoms.Normal articular cartilage maintains at aneural state.Neuron guidance factor Semaphorin 3A(Sema3A)is a membrane-associated secreted protein with chemorepulsive properties for axons.However,the role of Sema3A in articular cartilage is still not clear.In the present studies,we investigated the functions of Sema3A in OA development in mice,non-human primates,and patients with OA.Sema3A has a protective effect on cartilage degradation,validated by the organoid culture in vitro and confirmed in chondrocyte-specific Sema3A conditional knockout mice.We demonstrated that Sema3A is a key molecule in maintaining cartilage homeostasis from chondrocyte hypertrophy via activating the PI3K pathway.The potential usage of Sema3A for OA treatment was validated in mouse and Rhesus macaque OA models through intra-articular injection of Sema3A,and also in patients by administering Sema3A containing platelet-rich plasma into the knee joints.Our studies demonstrated that Sema3A exerts a critical role in inhibiting neurite ingrowth and preventing chondrocyte hypertrophy in cartilage,and could be potentially used for OA treatment.展开更多
本文通过综述的形式,论述了保守轴突导向因子Semaphorins的信号蛋白Semaphorins3F (Sema3F)的在神经系统中作用的研究。基于对Sema3F的概述,我们对神经的作用进行了系统总结。在神经发育的过程中,Sema3F作为调节因子,参与皮层椎体神经...本文通过综述的形式,论述了保守轴突导向因子Semaphorins的信号蛋白Semaphorins3F (Sema3F)的在神经系统中作用的研究。基于对Sema3F的概述,我们对神经的作用进行了系统总结。在神经发育的过程中,Sema3F作为调节因子,参与皮层椎体神经元树突密度的调节及诱导树突消除和树突细胞体的回缩等多种功能。同样在对Sema3F在感觉神经中的作用的研究中,我们发现其对于嗅觉系统、视觉、内耳和牙神经等有着重要的作用。本文还探讨了Sema3F对于包括自闭症、精神分裂症和癫痫等神经系统疾病的作用。我们认为,Sema3F在神经元的发育、感觉神经以及多种神经系统疾病中均起着重要的作用。This article, in the form of a review, discusses the research on the role of the semaphorin family member Semaphorin 3F (Sema3F), a conserved axon guidance molecule, in the nervous system. Based on an overview of Sema3F, we systematically summarize its effects on neurons. During the process of neural development, Sema3F acts as a regulatory factor, participating in the modulation of dendritic density in cortical pyramidal neurons, as well as inducing dendritic elimination and retraction of dendritic cell bodies, among other functions. Similarly, in studies on the role of Sema3F in sensory neurons, we have found that it plays an important role in the olfactory system, vision, inner ear, and dental nerves. The article also explores the role of Sema3F in various neurological disorders, including autism, schizophrenia, and epilepsy. We believe that Sema3F plays a significant role in the development of neurons, sensory neurons, and a variety of neurological diseases.展开更多
基金supported by Shenzhen University General Hospital Scientific Research Project,No.SUGH2019QD002Shenzhen Science and Technology Development Foundation,No.20220810173216001(both to ZS).
文摘Spinal cord injury is a severe neurological condition with limited neuronal regeneration and functional recovery.Currently,no effective treatments exist to improve spinal cord injury prognosis.Neuronal guidance proteins are a diverse group of molecules that play crucial roles in axon and dendrite growth during nervous system development.Increasing evidence highlights their regulatory functions in spinal cord injury.This review provides a brief overview of the modulation patterns of key neuronal guidance proteins in neuronal axon growth during nervous system formation and subsequently focuses on their roles in neuronal regeneration and functional recovery following spinal cord injury.Neuronal guidance proteins include,but are not limited to,semaphorins and their receptors,plexins;netrins and their receptors,deleted in colorectal cancer and UNC5;Eph receptors and their ligands,ephrins;Slit and its receptor,Robo;repulsive guidance molecules and their receptor,neogenin;Wnt proteins and their receptor,Frizzled;and protocadherins.Localized Netrin-1 at the injury site inhibits motor axon regeneration after adult spinal cord injury while promoting oligodendrocyte growth.Slit2 enhances synapse formation in the injured spinal cord of rats.EphA7 regulates acute apoptosis in the early pathophysiological stages of spinal cord injury,while ephrinA1 plays a role in the nervous system’s injury response,with its reduced expression leading to impaired motor function in rats.EphA3 is upregulated following spinal cord injury,promoting an inhibitory environment for axonal regeneration.After spinal cord injury,bidirectional activation of ephrinB2 and EphB2 in astrocytes and fibroblasts results in the formation of a dense astrocyte-meningeal fibroblast scar.EphB1/ephrinB1 signaling mediates pain processing in spinal cord injury by regulating calpain-1 and caspase-3 in neurons.EphB3 expression increases in white matter after spinal cord injury,further inhibiting axon regeneration.Sema3A,expressed by neurons and fibroblasts in the scar surrounding the injury,inhibits motor neuron and sensory nerve growth after spinal cord injury.Sema4D suppresses neuronal axon myelination and axon regeneration,while its inhibition significantly enhances axon regeneration and motor recovery.Sema7A is involved in glial scar formation and may influence serotonin channel remodeling,thereby affecting motor coordination.Given these findings,the local or systemic application of neuronal guidance proteins represents a promising avenue for spinal cord injury treatment.
文摘信号素(Semaphorin)作为一组多功能的蛋白质,占据神经系统功能发育的关键,包括对调节突触形成和神经元的生长的同时,还参与调控细胞周期、影响细胞形态的转变,以及在肿瘤学中,它们能够影响肿瘤细胞的生长、侵袭和转移,以及在免疫反应中发挥作用。信号素(Semaphorin, SEMA)是一类分泌型、膜结合型或糖磷脂酰肌醇锚定的糖蛋白,与神经发育、轴突引导、骨分化、心血管系统以及癌症等相关。Sema3F (Semaphorin 3F)是信号素家族轴突引导分子的一种分泌型,参与神经元的发育。Sema3F及其受体神经纤毛蛋白-2在胚胎小鼠大脑区域(包括嗅球、海马体和大脑皮层)中以互斥方式表达。Sema3F作用在神经元上,可引起下游因子的改变,包括CREBBP、CREB、VEGF等,能够下调P53表达、影响GABA能系统、下调RacGTP水平、促进CRMP2磷酸化等。本文通过综述的方法,对Sema3F在神经元下游因子进行叙述,为研究Sema3F在神经元中的功能提供帮助。Semaphorin, as a group of multifunctional proteins, plays a crucial role in the functional development of the nervous system. It not only regulates synapse formation and the growth of neurons but also participates in the regulation of the cell cycle, influences the transformation of cell morphology. Moreover, in oncology, it can affect the growth, invasion and metastasis of tumor cells and also plays a role in immune responses. Semaphorin (SEMA) is a type of secreted, membrane-bound or glycosylphosphatidylinositol-anchored glycoprotein, which is related to neural development, axon guidance, bone differentiation, the cardiovascular system and cancer, etc. Sema3F, a secreted form of the axon guidance molecules in the Semaphorin family, is involved in the development of neurons. Sema3F and its receptor neuropilin-2 are expressed in a mutually exclusive manner in the brain regions (including the olfactory bulb, hippocampus and cerebral cortex) of embryonic mice. When Sema3F acts on neurons, it can cause changes in downstream factors, including CREBBP, CREB, VEGF, etc. It can downregulate the expression of P53, affect the GABAergic system, downregulate the level of RacGTP and promote the phosphorylation of CRMP2, etc. Through the method of review, this article describes the downstream factors of Sema3F in neurons, aiming to provide assistance for the research on the functions of Sema3F in neurons.
基金partly National Key R&D Program of China(2023YFA1801200,2023YFA1801202)Major Program of the National Natural Science Foundation of China(T2394532)+6 种基金National Natural Science Foundation of China(82072489)The Foundation of Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(NYKFKT2019007)Shenzhen Medical Research Fund(B2302011)The Sanming Project of Medicine in Shenzhen(SZZYSM202311013)The China Postdoctoral Science Foundational,2023M743679Shenzhen Science and Technology Research Funding(JCYJ20220818101414032)Key Research Project of Science&Technology Department of Sichuan Province,China(2024YFFK0041)。
文摘Osteoarthritis(OA)is a degenerative joint disease accompanied with the loss of cartilage and consequent nociceptive symptoms.Normal articular cartilage maintains at aneural state.Neuron guidance factor Semaphorin 3A(Sema3A)is a membrane-associated secreted protein with chemorepulsive properties for axons.However,the role of Sema3A in articular cartilage is still not clear.In the present studies,we investigated the functions of Sema3A in OA development in mice,non-human primates,and patients with OA.Sema3A has a protective effect on cartilage degradation,validated by the organoid culture in vitro and confirmed in chondrocyte-specific Sema3A conditional knockout mice.We demonstrated that Sema3A is a key molecule in maintaining cartilage homeostasis from chondrocyte hypertrophy via activating the PI3K pathway.The potential usage of Sema3A for OA treatment was validated in mouse and Rhesus macaque OA models through intra-articular injection of Sema3A,and also in patients by administering Sema3A containing platelet-rich plasma into the knee joints.Our studies demonstrated that Sema3A exerts a critical role in inhibiting neurite ingrowth and preventing chondrocyte hypertrophy in cartilage,and could be potentially used for OA treatment.
文摘本文通过综述的形式,论述了保守轴突导向因子Semaphorins的信号蛋白Semaphorins3F (Sema3F)的在神经系统中作用的研究。基于对Sema3F的概述,我们对神经的作用进行了系统总结。在神经发育的过程中,Sema3F作为调节因子,参与皮层椎体神经元树突密度的调节及诱导树突消除和树突细胞体的回缩等多种功能。同样在对Sema3F在感觉神经中的作用的研究中,我们发现其对于嗅觉系统、视觉、内耳和牙神经等有着重要的作用。本文还探讨了Sema3F对于包括自闭症、精神分裂症和癫痫等神经系统疾病的作用。我们认为,Sema3F在神经元的发育、感觉神经以及多种神经系统疾病中均起着重要的作用。This article, in the form of a review, discusses the research on the role of the semaphorin family member Semaphorin 3F (Sema3F), a conserved axon guidance molecule, in the nervous system. Based on an overview of Sema3F, we systematically summarize its effects on neurons. During the process of neural development, Sema3F acts as a regulatory factor, participating in the modulation of dendritic density in cortical pyramidal neurons, as well as inducing dendritic elimination and retraction of dendritic cell bodies, among other functions. Similarly, in studies on the role of Sema3F in sensory neurons, we have found that it plays an important role in the olfactory system, vision, inner ear, and dental nerves. The article also explores the role of Sema3F in various neurological disorders, including autism, schizophrenia, and epilepsy. We believe that Sema3F plays a significant role in the development of neurons, sensory neurons, and a variety of neurological diseases.
