Biomaterial Database

ADF/Cofilin-Mediated Actin Turnover Promotes Axon Regeneration in the Adult CNS. 2019

Andrea Tedeschi, and Sebastian Dupraz, and Michele Curcio, and Claudia J Laskowski, and Barbara Schaffran, and Kevin C Flynn, and Telma E Santos, and Sina Stern, and Brett J Hilton, and Molly J E Larson, and Christine B Gurniak, and Walter Witke, and Frank Bradke

Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 27, 53127 Bonn, Germany.

Injured axons fail to regenerate in the adult CNS, which contrasts with their vigorous growth during embryonic development. We explored the potential of re-initiating axon extension after injury by reactivating the molecular mechanisms that drive morphogenetic transformation of neurons during development. Genetic loss- and gain-of-function experiments followed by time-lapse microscopy, in vivo imaging, and whole-mount analysis show that axon regeneration is fueled by elevated actin turnover. Actin depolymerizing factor (ADF)/cofilin controls actin turnover to sustain axon regeneration after spinal cord injury through its actin-severing activity. This pinpoints ADF/cofilin as a key regulator of axon growth competence, irrespective of developmental stage. These findings reveal the central role of actin dynamics regulation in this process and elucidate a core mechanism underlying axon growth after CNS trauma. Thereby, neurons maintain the capacity to stimulate developmental programs during adult life, expanding their potential for plasticity. Thus, actin turnover is a key process for future regenerative interventions.

UI	MeSH Term	Description	Entries
D009416	Nerve Regeneration	Renewal or physiological repair of damaged nerve tissue.	Nerve Tissue Regeneration,Nervous Tissue Regeneration,Neural Tissue Regeneration,Nerve Tissue Regenerations,Nervous Tissue Regenerations,Neural Tissue Regenerations,Regeneration, Nerve,Regeneration, Nerve Tissue,Regeneration, Nervous Tissue,Regeneration, Neural Tissue,Tissue Regeneration, Nerve,Tissue Regeneration, Nervous,Tissue Regeneration, Neural
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D000069416	Intravital Microscopy	Type of microscopy used to study biological systems at high resolution.	In Vivo Microscopy,Intravital Imaging,Imaging, Intravital,Microscopy, In Vivo,Microscopy, Intravital
D000199	Actins	Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.	F-Actin,G-Actin,Actin,Isoactin,N-Actin,alpha-Actin,alpha-Isoactin,beta-Actin,gamma-Actin,F Actin,G Actin,N Actin,alpha Actin,alpha Isoactin,beta Actin,gamma Actin
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001369	Axons	Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.	Axon
D013119	Spinal Cord Injuries	Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., WOUNDS, GUNSHOT; WHIPLASH INJURIES; etc.).	Myelopathy, Traumatic,Injuries, Spinal Cord,Post-Traumatic Myelopathy,Spinal Cord Contusion,Spinal Cord Laceration,Spinal Cord Transection,Spinal Cord Trauma,Contusion, Spinal Cord,Contusions, Spinal Cord,Cord Contusion, Spinal,Cord Contusions, Spinal,Cord Injuries, Spinal,Cord Injury, Spinal,Cord Laceration, Spinal,Cord Lacerations, Spinal,Cord Transection, Spinal,Cord Transections, Spinal,Cord Trauma, Spinal,Cord Traumas, Spinal,Injury, Spinal Cord,Laceration, Spinal Cord,Lacerations, Spinal Cord,Myelopathies, Post-Traumatic,Myelopathies, Traumatic,Myelopathy, Post-Traumatic,Post Traumatic Myelopathy,Post-Traumatic Myelopathies,Spinal Cord Contusions,Spinal Cord Injury,Spinal Cord Lacerations,Spinal Cord Transections,Spinal Cord Traumas,Transection, Spinal Cord,Transections, Spinal Cord,Trauma, Spinal Cord,Traumas, Spinal Cord,Traumatic Myelopathies,Traumatic Myelopathy
D051338	Cofilin 1	Cofilin 1 is a member of the cofilin family of proteins that is expressed in non-muscle CELLS. It has ACTIN depolymerization activity that is dependent on HYDROGEN-ION CONCENTRATION.	CFL1 Protein,N-Cofilin,Non-Muscle Cofilin,Cofilin, Non-Muscle,Non Muscle Cofilin
D051340	Cofilin 2	A member of the cofilin family of proteins that is expressed in MUSCLE CELLS. It has ACTIN depolymerization activity that is dependent on HYDROGEN-ION CONCENTRATION.	CFL2 Protein,Cofilin-2,M-Cofilin,Muscle Cofilin,Cofilin, Muscle
D051345	Destrin	A member of the actin depolymerizing factors. Its depolymerizing activity is independent of HYDROGEN-ION CONCENTRATION.	ADF Protein (Actin Depolymerizing Factor),Actin Depolymerizing Factor,DSTN Protein,Depolymerizing Factor, Actin