PTEN deletion enhances the regenerative ability of adult corticospinal neurons
Kai Liu,Yi Lu,Jae K. Lee,Ramsey F. Samara,Rafer Willenberg,Ilse Sears-Kraxberger,Andrea Tedeschi,Kevin K. Park,Duo Jin,Bin Cai,Bengang Xu,Lauren Connolly,Oswald Steward,Binhai Zheng,Zhigang He +14 more
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TLDR
It is found that PTEN/mTOR are critical for controlling the regenerative capacity of mouse corticospinal neurons and modulating neuronal intrinsic PTEN-mTOR activity represents a potential therapeutic strategy for promoting axon regeneration and functional repair after adult spinal cord injury.Abstract:
Despite the essential role of the corticospinal tract (CST) in controlling voluntary movements, successful regeneration of large numbers of injured CST axons beyond a spinal cord lesion has never been achieved. We found that PTEN/mTOR are critical for controlling the regenerative capacity of mouse corticospinal neurons. After development, the regrowth potential of CST axons was lost and this was accompanied by a downregulation of mTOR activity in corticospinal neurons. Axonal injury further diminished neuronal mTOR activity in these neurons. Forced upregulation of mTOR activity in corticospinal neurons by conditional deletion of Pten, a negative regulator of mTOR, enhanced compensatory sprouting of uninjured CST axons and enabled successful regeneration of a cohort of injured CST axons past a spinal cord lesion. Furthermore, these regenerating CST axons possessed the ability to reform synapses in spinal segments distal to the injury. Thus, modulating neuronal intrinsic PTEN/mTOR activity represents a potential therapeutic strategy for promoting axon regeneration and functional repair after adult spinal cord injury.read more
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Long-Distance Growth and Connectivity of Neural Stem Cells after Severe Spinal Cord Injury
Paul Lu,Yaozhi Wang,Lori Graham,Karla McHale,Mingyong Gao,Di Wu,John H. Brock,Armin Blesch,Armin Blesch,Ephron S. Rosenzweig,Leif A. Havton,Binhai Zheng,James M. Conner,Martin Marsala,Mark H. Tuszynski,Mark H. Tuszynski +15 more
TL;DR: Property intrinsic to early-stage neurons can overcome the inhibitory milieu of the injured adult spinal cord to mount remarkable axonal growth, resulting in formation of new relay circuits that significantly improve function.
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From basics to clinical: a comprehensive review on spinal cord injury.
TL;DR: An extensive overview of SCI research, as well as its clinical component, is provided, covering areas from physiology and anatomy of the spinal cord, neuropathology of the SCI, current clinical options, neuronal plasticity after SCI and a variety of promising neuroprotective, cell-based and combinatorial therapeutic approaches that have recently moved, or are close to clinical testing.
Journal ArticleDOI
Functional regeneration beyond the glial scar.
Jared M. Cregg,Marc A. DePaul,Angela R. Filous,Bradley T. Lang,Amanda Phuong Tran,Jerry Silver +5 more
TL;DR: Evidence that this aggregate scar acts as the major barrier to regeneration of axons after injury is reviewed and several exciting new interventions that allow axons to regenerate beyond the glial scar are considered.
Journal ArticleDOI
Intrinsic Control of Axon Regeneration
Zhigang He,Yishi Jin +1 more
TL;DR: In this paper, the authors examine the current understanding of axon regeneration mechanisms at cellular and molecular terms and discuss their potential implications for promoting axon recovery and functional recovery after nerve injury.
Journal ArticleDOI
Neuronal Intrinsic Mechanisms of Axon Regeneration
TL;DR: It is suggested that blocking extracellular inhibitory influences alone is insufficient to allow the majority of injured axons to regenerate, pointing to the importance of revisiting the hypothesis that diminished intrinsic regeneration ability critically underlies regeneration failure.
References
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TL;DR: The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model and the regenerative potential of these central neurons seems to be expressed when the central nervous System glial environment is changed to that of the peripheral nervous system.
Journal ArticleDOI
Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR Pathway
Kevin K. Park,Kai Liu,Yang Hu,Patrice D. Smith,Chen Wang,Bin Cai,Bengang Xu,Lauren Connolly,Ioannis Kramvis,Mustafa Sahin,Zhigang He +10 more
TL;DR: The manipulation of intrinsic growth control pathways as a therapeutic approach to promote axon regeneration after CNS injury is suggested.
Journal ArticleDOI
Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors.
Lisa Schnell,Martin E. Schwab +1 more
TL;DR: The capacity for CNS axons to regenerate and elongate within differentiated CNS tissue after the neutralization of myelin-associated neurite growth inhibitors is demonstrated.
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Neuronal Subtype-Specific Genes that Control Corticospinal Motor Neuron Development In Vivo
TL;DR: Loss-of-function experiments in null mutant mice for Ctip2 (also known as Bcl11b), one of the newly characterized genes, demonstrate that it plays a critical role in the development of CSMN axonal projections to the spinal cord in vivo, confirming that the central genetic determinants of the CSMN population are identified.