Promoting axon regeneration in the central nervous system by increasing PI3-kinase signaling

Much research has focused on the PI3-kinase and PTEN signaling pathway with the aim to stimulate repair of the injured central nervous system. Axons in the central nervous system fail to regenerate, meaning that injuries or diseases that cause loss of axonal connectivity have life-changing consequen...

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Autores principales:	Bart Nieuwenhuis, Richard Eva
Formato:	article
Lenguaje:	EN
Publicado:	Wolters Kluwer Medknow Publications 2022
Materias:	axon cytoskeleton; axon regeneration; axon transport; cell signaling; central nervous system; growth cone; neuroprotection; pi3-kinase; pi3k; pten; trafficking; transcription; translation Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/09df2801689441b7b7d61c9a33688594
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spelling	oai:doaj.org-article:09df2801689441b7b7d61c9a336885942021-11-19T12:16:44ZPromoting axon regeneration in the central nervous system by increasing PI3-kinase signaling1673-537410.4103/1673-5374.327324https://doaj.org/article/09df2801689441b7b7d61c9a336885942022-01-01T00:00:00Zhttp://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=6;spage=1172;epage=1182;aulast=Nieuwenhuishttps://doaj.org/toc/1673-5374Much research has focused on the PI3-kinase and PTEN signaling pathway with the aim to stimulate repair of the injured central nervous system. Axons in the central nervous system fail to regenerate, meaning that injuries or diseases that cause loss of axonal connectivity have life-changing consequences. In 2008, genetic deletion of PTEN was identified as a means of stimulating robust regeneration in the optic nerve. PTEN is a phosphatase that opposes the actions of PI3-kinase, a family of enzymes that function to generate the membrane phospholipid PIP3 from PIP2 (phosphatidylinositol (3,4,5)-trisphosphate from phosphatidylinositol (4,5)-bisphosphate). Deletion of PTEN therefore allows elevated signaling downstream of PI3-kinase, and was initially demonstrated to promote axon regeneration by signaling through mTOR. More recently, additional mechanisms have been identified that contribute to the neuron-intrinsic control of regenerative ability. This review describes neuronal signaling pathways downstream of PI3-kinase and PIP3, and considers them in relation to both developmental and regenerative axon growth. We briefly discuss the key neuron-intrinsic mechanisms that govern regenerative ability, and describe how these are affected by signaling through PI3-kinase. We highlight the recent finding of a developmental decline in the generation of PIP3 as a key reason for regenerative failure, and summarize the studies that target an increase in signaling downstream of PI3-kinase to facilitate regeneration in the adult central nervous system. Finally, we discuss obstacles that remain to be overcome in order to generate a robust strategy for repairing the injured central nervous system through manipulation of PI3-kinase signaling.Bart NieuwenhuisRichard EvaWolters Kluwer Medknow Publicationsarticleaxon cytoskeleton; axon regeneration; axon transport; cell signaling; central nervous system; growth cone; neuroprotection; pi3-kinase; pi3k; pten; trafficking; transcription; translationNeurology. Diseases of the nervous systemRC346-429ENNeural Regeneration Research, Vol 17, Iss 6, Pp 1172-1182 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	axon cytoskeleton; axon regeneration; axon transport; cell signaling; central nervous system; growth cone; neuroprotection; pi3-kinase; pi3k; pten; trafficking; transcription; translation Neurology. Diseases of the nervous system RC346-429
spellingShingle	axon cytoskeleton; axon regeneration; axon transport; cell signaling; central nervous system; growth cone; neuroprotection; pi3-kinase; pi3k; pten; trafficking; transcription; translation Neurology. Diseases of the nervous system RC346-429 Bart Nieuwenhuis Richard Eva Promoting axon regeneration in the central nervous system by increasing PI3-kinase signaling
description	Much research has focused on the PI3-kinase and PTEN signaling pathway with the aim to stimulate repair of the injured central nervous system. Axons in the central nervous system fail to regenerate, meaning that injuries or diseases that cause loss of axonal connectivity have life-changing consequences. In 2008, genetic deletion of PTEN was identified as a means of stimulating robust regeneration in the optic nerve. PTEN is a phosphatase that opposes the actions of PI3-kinase, a family of enzymes that function to generate the membrane phospholipid PIP3 from PIP2 (phosphatidylinositol (3,4,5)-trisphosphate from phosphatidylinositol (4,5)-bisphosphate). Deletion of PTEN therefore allows elevated signaling downstream of PI3-kinase, and was initially demonstrated to promote axon regeneration by signaling through mTOR. More recently, additional mechanisms have been identified that contribute to the neuron-intrinsic control of regenerative ability. This review describes neuronal signaling pathways downstream of PI3-kinase and PIP3, and considers them in relation to both developmental and regenerative axon growth. We briefly discuss the key neuron-intrinsic mechanisms that govern regenerative ability, and describe how these are affected by signaling through PI3-kinase. We highlight the recent finding of a developmental decline in the generation of PIP3 as a key reason for regenerative failure, and summarize the studies that target an increase in signaling downstream of PI3-kinase to facilitate regeneration in the adult central nervous system. Finally, we discuss obstacles that remain to be overcome in order to generate a robust strategy for repairing the injured central nervous system through manipulation of PI3-kinase signaling.
format	article
author	Bart Nieuwenhuis Richard Eva
author_facet	Bart Nieuwenhuis Richard Eva
author_sort	Bart Nieuwenhuis
title	Promoting axon regeneration in the central nervous system by increasing PI3-kinase signaling
title_short	Promoting axon regeneration in the central nervous system by increasing PI3-kinase signaling
title_full	Promoting axon regeneration in the central nervous system by increasing PI3-kinase signaling
title_fullStr	Promoting axon regeneration in the central nervous system by increasing PI3-kinase signaling
title_full_unstemmed	Promoting axon regeneration in the central nervous system by increasing PI3-kinase signaling
title_sort	promoting axon regeneration in the central nervous system by increasing pi3-kinase signaling
publisher	Wolters Kluwer Medknow Publications
publishDate	2022
url	https://doaj.org/article/09df2801689441b7b7d61c9a33688594
work_keys_str_mv	AT bartnieuwenhuis promotingaxonregenerationinthecentralnervoussystembyincreasingpi3kinasesignaling AT richardeva promotingaxonregenerationinthecentralnervoussystembyincreasingpi3kinasesignaling
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Promoting axon regeneration in the central nervous system by increasing PI3-kinase signaling

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