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- Title
PTEN deletion enhances the regenerative ability of adult corticospinal neurons.
- Authors
Kai Liu; Yi Lu; Lee, Jae K.; Samara, Ramsey; Willenberg, Rafer; Sears-Kraxberger, Ilse; Tedeschi, Andrea; Park, Kevin Kyungsuk; Duo Jin; Bin1Cai; Bengang Xu; Connolly, Lauren; Steward, Oswald; Binhai Zheng; Zhigang He
- 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.
- Publication
Nature Neuroscience, 2010, Vol 13, Issue 9, p1075
- ISSN
1097-6256
- Publication type
Academic Journal
- DOI
10.1038/nn.2603