PTEN Blocking Stimulates Corticospinal and Raphespinal Axonal Regeneration and Promotes Functional Recovery After Spinal Cord Injury.

Abstract:

:The long-term disabilities associated with spinal cord injury (SCI) are primarily due to the absence of robust neuronal regeneration and functional plasticity. The inability of the axon to regenerate after SCI is contributed by several intrinsic factors that trigger a cascade of molecular growth program and modulates axonal sprouting. Phosphatase and tensin homolog (PTEN) is one of the intrinsic factors contributing to growth failure after SCI, however, the underlying mechanism is not well known. Here, we developed a novel therapeutic approach for treating SCI by suppressing the action of PTEN in a mouse model of hemisection SCI. We have used a novel peptide, PTEN antagonistic peptide (PAP) to block the critical domains of PTEN to demonstrate its ability to potentially promote axon growth. PAP treatment not only enhanced regeneration of corticospinal axons into the caudal spinal cord but also promoted the regrowth of descending serotonergic axons in SCI mice. Furthermore, expression levels of p-mTOR, p-S6, p-Akt, p-Erk, p-GSK, p-PI3K downstream of PTEN signaling pathway were increased significantly in the spinal cord of SCI mice systemically treated with PAP than control TAT peptide-treated mice. Our novel strategy of administering deliverable compounds postinjury may facilitate translational feasibility for central nervous system injury.

authors

Bhowmick S,Abdul-Muneer PM

doi

10.1093/jnen/nlaa147

subject

Has Abstract

pub_date

2021-01-20 00:00:00

pages

169-181

issue

2

eissn

0022-3069

issn

1554-6578

pii

6049045

journal_volume

80

pub_type

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