摘要
Following nerve injury,axonal disconnection in neurons usually results in persistent functional deficits,such as paralysis.However,axons in the adult mammalian central nervous system (CNS) have very limited regenerative ability.Understanding the molecular mechanism of controlling axon regeneration can provide idea for the design of effective therapeutic interventions for CNS injury,such as spinal cord injuries.Efficient axonal regeneration is achieved via gene expression in the neuronal soma,axonal transport of raw materials along the shaft,and membrane and cytoskeleton assembly at the nerve growth cone.Each process is delicately regulated by spatial-temporal controlled signaling pathways that target distinct effectors.Gene expression in the neuronal soma,especially of transcription factors,is often activated immediately following nerve injury.Injury signals at distal axons are interpreted and transmitted back to the soma,initiating a stream of gene expression events which positively regulate subsequent axonal regeneration.Over the past few decades,extensive studies have identified many regeneration-associated genes,including CREB,nuclear factor of activated T-cells,protein 53,Sprr1a,c-Jun,Smad1,activating transcription factor 3,signal transducer and activator of transcription 3,SRF,Sox11,and Kruppel-like factors.However,we know far less about how the coordinated expression of these regeneration-associated genes is regulated during axonal regeneration.Indeed,it is possible that they are regulated by a single common upstream regulator.If so,identification of this upstream regulator will provide us with an invaluable target for the development of more effective treatments for traumatic nerve injuries.Adult dorsal root ganglion (DRG) neurons represent a favorable medium in which to study the molecular mechanisms controlling intrinsic neuronal axon growth ability.Axotomy of the peripheral branch of a DRG neuron,known as a “conditioning lesion”,has been well-documented to greatly accelerate axonal growth both in vivo and in vitro,by enhancing the neuronal intrinsic growth potential.Enhancement of the growth state is thought to be mediated by a transcription-dependent axonal growth system that controls the expression of a number of regeneration-associated genes.
基金
supported by the National Natural Science Foundation of China (Nos.81772353 and 81571189)
the National Key Research and Development Program (No.2016YFC 1100203)
the Priority Academic Program Development of Jiangsu Higher Education Institutions,and Innovation and Entrepreneurship Program of Jiangsu Province of China.