AKT-dependent and -independent pathways mediate PTEN deletion-induced CNS axon regeneration.

Cell Death & Disease
Haoliang HuangYang Hu

Abstract

Phosphatase and tensin homolog (PTEN) acts as a brake for the phosphatidylinositol 3-kinase-AKT-mTOR complex 1 (mTORC1) pathway, the deletion of which promotes potent central nervous system (CNS) axon regeneration. Previously, we demonstrated that AKT activation is sufficient to promote CNS axon regeneration to a lesser extent than PTEN deletion. It is still questionable whether AKT is entirely responsible for the regenerative effect of PTEN deletion on CNS axons. Here, we show that blocking AKT or its downstream effectors, mTORC1 and GSK3β, significantly reduces PTEN deletion-induced mouse optic nerve regeneration, indicating the necessary role of AKT-dependent signaling. However, AKT is only marginally activated in PTEN-null mice due to mTORC1-mediated feedback inhibition. That combining PTEN deletion with AKT overexpression or GSK3β deletion achieves significantly more potent axonal regeneration suggests an AKT-independent pathway for axon regeneration. Elucidating the AKT-independent pathway is required to develop effective strategies for CNS axon regeneration.

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Citations

Oct 15, 2019·Restorative Neurology and Neuroscience·Yuqin YinLarry I Benowitz
Dec 10, 2020·Molecular Therapy. Nucleic Acids·Nanxiang WangLimin Rong
Feb 6, 2021·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Juliana Ferreira VasquesAdriana da Cunha Faria-Melibeu
Jun 2, 2021·Disease Models & Mechanisms·María Losada-PérezSergio Casas-Tintó
Aug 28, 2021·International Journal of Molecular Sciences·Toshiyuki Oshitari

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Methods Mentioned

BETA
dissection
density-gradient centrifugation
PCR

Software Mentioned

GraphPad Prism

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AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.