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Publications on PTEN Inhibition and Nerve Regeneration

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Publications on PTEN inhibition and nerve regeneration

Neuronal PTEN deletion in adult cortical neurons triggers progressive growth of cell bodies, dendrites, and axons

Gallent, E. and Steward, O. (2018).   Exp. Neurol., 303, 12-28.
Robust neuronal growth can be induced in fully mature cortical neurons long after the developmental period has ended and that this continuous growth occurs without obvious functional impairments.

Modest enhancement of sensory axon regeneration in the sciatic nerve with conditional co-deletion of PTEN and SOCS3 in the dorsal root ganglia of adult mice

Gallaher, Z.R., and Steward, O.  (2018) Exp. Neurol., 303, 120-133
Co-deletion of PTEN and SOCS3 results in modest but measureable enhancement of early regeneration of Dorsal Root Ganglion axons following crush injury.

Selective neuronal PTEN deletion: Can we take the brakes off of growth without losing control?

Gutilla, E. A., and Steward, O. (2016)  Neural Regeneration Research. 11(8): 1201–1203.
The long-term deletion of PTEN in mature neurons does not cause macrocephaly, seizures, and early mortality. Cortical neurons that have lived without PTEN for over one year appear robust and healthy.

Long-term consequences of conditional genetic deletion of PTEN in the sensorimotor cortex of neonatal mice

article-thumb-experimental-neurology-2016Eriin Gutilla, Oswald Steward, Experimental Neurology 2016
PTEN inhibition causes the growth of axons. Uncontrolled cell growth is cancer. Dr. Steward wanted to find out if inhibiting PTEN causes tumors to form. Dr. Steward inhibited PTEN in the cortex of one day old rats and allowed them to survive 18 months. A rat’s average lifespan is 24 months. No tumors formed in the rats that received PTEN treatment and lived for 18 months.

PTEN Deletion Promotes Regrowth of Corticospinal Tract Axons 1 Year after Spinal Cord Injury

article-journal-neuroscience-2015Kaimeng Du,et al, Journal of Neuroscience July 2015
Dr. Liu is the first author on the 2010 Nature Neuroscience article which described regeneration in the corrticospinal tract for the first time in history. At the time Dr. Liu was a post doctoral reseacher in Zhigang He’s lab at Harvard University. Dr. Liu set up his own lab at Hong Kong University. He has been studying PTEN inhibition in chronic spinal cord injury. In this current article from Journal of Neuroscience, Dr. Liu shows robust regeneration at seven months after PTEN inhibition in chronic spinal cord injured mice.

Conditional genetic deletion of PTEN after a spinal cord injury enhances regenerative growth of CST axons and motor function recovery in mice

article-experimental-neuology-2015Camelia A. Danilov, Oswald Steward, Experimental Neurology 2015
This article from Experimental Neurology explains how Dr. Steward blocked PTEN in the left fore paw of acutely injured mice, which caused a recovery of function to better than normal compared to the uninjured paw.  The injured paw which received PTEN treatment was exercised throughout the experiment.  The uninjured fore paw was not exercised.

AAVshRNA-Mediated Suppression of PTEN in Adult Rats in Combination with Salmon Fibrin Administration Enables Regenerative Growth of Corticospinal Axons and Enhances Recovery of Voluntary Motor Function after Cervical Spinal Cord Injury

article-journal-neuroscience-2014Gail Lewandowski and Oswald Steward, Journal of Neuroscience July 2014
This is the first paper to show recovery in acutely injured rats that received PTEN inhibition. Dr. Stewart blocked PTEN in the rat’s brain and a manipulated the injury site with salmon fibrin, a natural glue, to encourage the growth of CSTS axons into and through the injury site. The rats that received PTEN inhibition experienced a recovery in their fore paws to 95% of normal.

PTEN deletion enhances the regenerative ability of adult corticospinal neurons

Liu et al., Nature Neuroscience, September 2010
This is the paper that was published in the September 2010 Nature Neuroscience. Nature is the leading science journal in the world. Papers published in Nature undergo the highest level of scrutiny and peer review. A photo of the nerve regeneration achieved by Drs. He and Steward made the cover of the September 2010 issue.

Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR Pathway

Park et al., Science, November 2008
This is the 2008 seminal article by Dr. He showing that PTEN inhibition causes regeneration in the optic nerve. Optic nerve is a simplier system than the spinal cord. This is why Dr. He chose to work in the optic nerve first. The article was published in Science, the leading U.S. science journal.

Other articles about PTEN Inhibiton

Pten ablation in adult dopaminergic neurons is neuroprotective in Parkinson’s disease models

article-thumb-faseb-journal-2011Domanskyi et al, FASEB Journal, 2011
Dr. Domansky ablated PTEN in a mouse model of Parkinson’s disease, which prevented the mice from developing Parkinson’s disease.

Sustained axon regeneration induced by co-deletion of PTEN and SOCS3

Sun, et al., Nature 2011
Dr. He combined inhibition of PTEN and SOCS3 to cause four times the number of axons to regenerate which grew 10 times the distance of PTEN or SOCS3 deletion individually.

PTEN Inhibition to Facilitate Intrinsic Regenerative Outgrowth of Adult Peripheral Axons

Christie et al., The Journal of Neuroscience, July 7, 2010
In this paper, a Canadian neuroscientist, Doug Zochodne, shows that PTEN inhibition can cause regeneration of the nerves in the arms and legs.

SOCS3 Deletion Promotes Optic Nerve Regeneration In Vivo

Smith et al., Neuron (2009)
Dr. He has discovered that inhibiting another pathway, SOCS3, also promotes nerve regeneration. Dr. He postulates that SOCS3 starts the regeneration and PTEN greatly increases the regeneration.

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