title: Autophagy induction stabilizes microtubules and promotes axon regeneration after spinal cord injury.
abstract: Remodeling of cytoskeleton structures, such as microtubule assembly, is believed to be crucial for growth cone initiation and regrowth of injured axons. Autophagy plays important roles in maintaining cellular homoeostasis, and its dysfunction causes neuronal degeneration. The role of autophagy in axon regeneration after injury remains speculative. Here we demonstrate a role of autophagy in regulating microtubule dynamics and axon regeneration. We found that autophagy induction promoted neurite outgrowth, attenuated the inhibitory effects of nonpermissive substrate myelin, and decreased the formation of retraction bulbs following axonal injury in cultured cortical neurons. Interestingly, autophagy induction stabilized microtubules by degrading SCG10, a microtubule disassembly protein in neurons. In mice with spinal cord injury, local administration of a specific autophagy-inducing peptide, Tat-beclin1, to lesion sites markedly attenuated axonal retraction of spinal dorsal column axons and cortical spinal tract and promoted regeneration of descending axons following long-term observation. Finally, administration of Tat-beclin1 improved the recovery of motor behaviors of injured mice. These results show a promising effect of an autophagy-inducing reagent on injured axons, providing direct evidence supporting a beneficial role of autophagy in axon regeneration.
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yuetong
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Institute of Biochemistry and Cell Biology, State Key Laboratory of Molecular Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chu
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tang
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China zgluo@ion.ac.cn.
authors.forename: Zhen-Ge
authors.initials: ZG
authors.lastname: Luo
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D000071186:Beclin-1 / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism; D002135:Calcium-Binding Proteins; D020439:Growth Cones / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D009416:Nerve Regeneration; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D013116:Spinal Cord / Q000254:growth & development / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D050777:Stathmin
chemical_list: D000071186:Beclin-1; D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D050777:Stathmin; C512849:Stmn2 protein, mouse
keywords: autophagy; axon regeneration; microtubule stabilization