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Neural Regeneration Research 2022年第6期17卷 1172-1182页

作者： Bart Nieuwenhuis Richard Eva John van Geest Center for Brain Repair Department of Clinical NeurosciencesUniversity of CambridgeCambridgeUK

Much research has focused on the PI3-kinase and PTEN signaling pathway with the aim to stimulate repair of the injured central nervous *** in the central nervous system fail to regenerate,meaning that injuries or diseases that cause loss of axonal connectivity have life-changing *** 2008,genetic deletion of PTEN was identified as a means of stimulating robust regeneration in the optic *** is a phosphatase that opposes the actions of PI3-kinase,a family of enzymes that function to generate the membrane phospholipid PIP_(3) from PIP_(2)(phosphatidylinositol(3,4,5)-trisphosphate from phosphatidylinositol(4,5)-bisphosphate).Deletion of PTEN therefore allows elevated signaling downstream of PI3-kinase,and was initially demonstrated to promote axon regeneration by signaling through *** recently,additional mechanisms have been identified that contribute to the neuron-intrinsic control of regenerative *** review describes neuronal signaling pathways downstream of PI3-kinase and PIP3,and considers them in relation to both developmental and regenerative axon *** briefly discuss the key neuron-intrinsic mechanisms that govern regenerative ability,and describe how these are affected by signaling through *** highlight the recent finding of a developmental decline in the generation of PIP_(3) as a key reason for regenerative failure,and summarize the studies that target an increase in signaling downstream of PI3-kinase to facilitate regeneration in the adult central nervous ***,we discuss obstacles that remain to be overcome in order to generate a robust strategy for repairing the injured central nervous system through manipulation of PI3-kinase signaling.

关键词： axon cytoskeleton axon regeneration axon transport cell signaling central nervous system growth cone neuroprotection PI3-kinase PI3K PTEN trafficking transcription translation

Cathepsins in neuronal plasticity

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Neural Regeneration Research 2021年第1期16卷 26-35页

作者： Amanda Phuong Tran Jerry Silver Center for Integrative Brain Research Seattle Children’s Research InstituteSeattleWAUSA Department of Neurosciences Case Western Reserve UniversityClevelandOHUSA

Proteases comprise a variety of enzymes defined by their ability to catalytically hydrolyze the peptide bonds of other proteins,resulting in protein ***,specifically,encompass a class of at least twenty proteases with potent endopeptidase *** are located subcellularly in lysosomes,organelles responsible for the cell’s degradative and autophagic processes,and are vital for normal lysosomal *** cathepsins are involved in a multitude of cell signaling activities,this chapter will focus on the role of cathepsins(with a special emphasis on Cathepsin B)in neuronal *** will broadly define what is known about regulation of cathepsins in the central nervous system and compare this with their dysregulation after injury or ***,we will delineate what is currently known about the role of cathepsins in axon regeneration and plasticity after spinal cord *** is well established that normal cathepsin activity is integral to the function of *** normal lysosomal function,autophagy and other homeostatic cellular processes become dysregulated resulting in axon ***,controlled activation of cathepsins at specialized neuronal structures such as axonal growth cones and dendritic spines have been positively implicated in their *** chapter will end with a perspective on the consequences of cathepsin dysregulation versus controlled,localized regulation to clarify how cathepsins can contribute to both neuronal plasticity and neurodegeneration.

关键词： axon regeneration cathepsin CSPGs extracellular matrix growth cone lysosomes neuronal plasticity protease remodeling spinal cord injury synaptogenesis

Chromophore-assisted laser inactivation in neural development

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Neuroscience Bulletin 2012年第4期28卷 333-341页

作者： Wei Li Nico Stuurman Guangshuo Ou National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China The Howard Hughes Medical Institute and the Department of Cellular and Molecular Pharmacology University ofCalifornia San Francisco San Francisco CA 94158 USA

Chromophore-assisted laser inactivation（CALI） is a technique that uses photochemically-generated reactive oxygen species to acutely inactivate target proteins in living *** development includes highly dynamic cellular processes such as asymmetric cell division,migration,axon and dendrite outgrowth and *** many key molecules of neural development have been identified since the past decades,their spatiotemporal contributions to these cellular events are not well *** provides an appealing tool for elucidating the precise functions of these molecules during neural *** this review,we summarize the principles of CALI,a recent microscopic setup to perform CALI experiments,and the application of CALI to the study of growth-cone motility and neuroblast asymmetric division.

关键词： chromophore-assisted laser inactivation growth cone neuroblast asymmetric cell division

Microtubule dynamics in axon guidance

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Neuroscience Bulletin 2014年第4期30卷 569-583页

作者： Guofa Liu Trisha Dwyer Department of Biological Sciences University of Toledo ToledoOH 43606USA

Precise modulation of the cytoskeleton is involved in a variety of cellular processes including cell division, migration, polarity, and adhesion. In developing post-mitotic neurons, extracellular guidance cues not only trigger signaling cascades that act at a distance to indirectly regulate microtubule distribution, and assembly and disassembly in the growth cone, but also directly modulate microtubule stability and dynamics through coupling of guidance receptors with microtubules to control growth-cone turning. Microtubule-associated proteins including classical microtubule-associated proteins and microtubule plus-end tracking proteins are required for modulating microtubule dynamics to influence growth-cone steering. Multiple key signaling components, such as calcium, small GTPases, glycogen synthase kinase-313, and c-Jun N-terminal kinase, link upstream signal cascades to microtubule stability and dynamics in the growth cone to control axon outgrowth and projection. Understanding the functions and regulation of microtubule dynamics in the growth cone provides new insights into the molecular mechanisms of axon guidance.

关键词： axon guidance growth cone microtubule dynamics signal transduction

Substrate topography affects PC12 cell differentiation through mechanotransduction mechanisms

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Mechanobiology in Medicine 2024年第1期2卷 86-96页

作者： Papadimitriou, Lina Karagiannaki, Anna Stratakis, Emmanuel Ranella, Anthi Institute of Electronic Structure and Laser Foundation for Research and Technology-Hellas (FORTH) Heraklion 71003 Greece Department of Physics University of Crete Heraklion 71003 Greece

Neural stem cells in vivo receive information from biochemical and biophysical cues of their microenvironment that affect their survival, proliferation and differentiation toward specific lineages. Recapitulation of these conditions in vitro is better achieved in 3D cell cultures. Especially the cells that grow in scaffold-dependent 3D cultures establish more complex cell–cell and cell–material interactions enabling the study of the various signaling pathways. The biochemical signaling from growth factors and hormones has been extensively studied over the years. More recently cumulative evidence demonstrates that cell sensing and response to mechanical stimuli is mediated through mechanotransduction pathways. Although individual signaling pathways activated by biochemical or mechanical cues in cells are well-studied, synergistic or antagonistic effects among them need further research to be fully understood. The understanding of the alteration of the cell behavior due to a microenvironmental cues would be greatly enhanced by the study of key elements that lie in the convergence of biochemical and mechanical pathways. Here we analyzed the effect of the substrate topography on the nerve growth factor (NGF) induced differentiation of PC12 cells. Our results showed that the topography interferes with NGF-induced neuronal differentiation and this is reflected in the reduced activation of the integrin-mediated mechanotransduction. © 2024

关键词： Focal adhesion growth cone Laser pattern topography Mechanotrunsduction Neural differentiation