Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control?
The limited ability for injured adult axons to regenerate is a major cause for limited functional recovery after injury to the nervous system, motivating numerous efforts to uncover mechanisms capable of enhancing regeneration potential. One promising strategy involves deletion or knockdown of the p...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2016-01-01
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| Series: | Neural Regeneration Research |
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| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2016;volume=11;issue=8;spage=1201;epage=1203;aulast=Gutilla |
| _version_ | 1818118221453066240 |
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| author | Erin A Gutilla Oswald Steward |
| author_facet | Erin A Gutilla Oswald Steward |
| author_sort | Erin A Gutilla |
| collection | DOAJ |
| description | The limited ability for injured adult axons to regenerate is a major cause for limited functional recovery after injury to the nervous system, motivating numerous efforts to uncover mechanisms capable of enhancing regeneration potential. One promising strategy involves deletion or knockdown of the phosphatase and tensin (PTEN) gene. Conditional genetic deletion of PTEN before, immediately following, or several months after spinal cord injury enables neurons of the corticospinal tract (CST) to regenerate their axons across the lesion, which is accompanied by enhanced recovery of skilled voluntary motor functions mediated by the CST. Although conditional genetic deletion or knockdown ofPTEN in neurons enables axon regeneration, PTEN is a well-known tumor suppressor and mutations of the PTEN gene disrupt brain development leading to neurological abnormalities including macrocephaly, seizures, and early mortality. The long-term consequences of manipulating PTEN in the adult nervous system, as would be done for therapeutic intervention after injury, are only now being explored. Here, we summarize evidence indicating that long-term deletion of PTEN in mature neurons does not cause evident pathology; indeed, cortical neurons that have lived without PTEN for over 1 year appear robust and healthy. Studies to date provide only a first look at potential negative consequences of PTEN deletion or knockdown, but the absence of any detectable neuropathology supports guarded optimism that interventions to enable axon regeneration after injury are achievable. |
| first_indexed | 2024-12-11T04:50:51Z |
| format | Article |
| id | doaj.art-10a42b0931ba42d3b857809689e645c6 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-12-11T04:50:51Z |
| publishDate | 2016-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-10a42b0931ba42d3b857809689e645c62022-12-22T01:20:24ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742016-01-011181201120310.4103/1673-5374.189160Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control?Erin A GutillaOswald StewardThe limited ability for injured adult axons to regenerate is a major cause for limited functional recovery after injury to the nervous system, motivating numerous efforts to uncover mechanisms capable of enhancing regeneration potential. One promising strategy involves deletion or knockdown of the phosphatase and tensin (PTEN) gene. Conditional genetic deletion of PTEN before, immediately following, or several months after spinal cord injury enables neurons of the corticospinal tract (CST) to regenerate their axons across the lesion, which is accompanied by enhanced recovery of skilled voluntary motor functions mediated by the CST. Although conditional genetic deletion or knockdown ofPTEN in neurons enables axon regeneration, PTEN is a well-known tumor suppressor and mutations of the PTEN gene disrupt brain development leading to neurological abnormalities including macrocephaly, seizures, and early mortality. The long-term consequences of manipulating PTEN in the adult nervous system, as would be done for therapeutic intervention after injury, are only now being explored. Here, we summarize evidence indicating that long-term deletion of PTEN in mature neurons does not cause evident pathology; indeed, cortical neurons that have lived without PTEN for over 1 year appear robust and healthy. Studies to date provide only a first look at potential negative consequences of PTEN deletion or knockdown, but the absence of any detectable neuropathology supports guarded optimism that interventions to enable axon regeneration after injury are achievable.http://www.nrronline.org/article.asp?issn=1673-5374;year=2016;volume=11;issue=8;spage=1201;epage=1203;aulast=GutillaPTEN; mTOR; spinal cord injury; corticospinal tract; motor system; axon regeneration; recovery of function |
| spellingShingle | Erin A Gutilla Oswald Steward Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control? Neural Regeneration Research PTEN; mTOR; spinal cord injury; corticospinal tract; motor system; axon regeneration; recovery of function |
| title | Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control? |
| title_full | Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control? |
| title_fullStr | Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control? |
| title_full_unstemmed | Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control? |
| title_short | Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control? |
| title_sort | selective neuronal pten deletion can we take the brakes off of growth without losing control |
| topic | PTEN; mTOR; spinal cord injury; corticospinal tract; motor system; axon regeneration; recovery of function |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2016;volume=11;issue=8;spage=1201;epage=1203;aulast=Gutilla |
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