Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway (Science, 2008, 322:963-966)

報告日期: 2009/05/08
報告時間: 15:10/16:00
報告學生: 蕭雅心
講評老師: 許鍾瑜
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980508-1.pdf

Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR Pathway

 

Kevin Kyungsuk Park, Kai Liu, Yang Hu, Patrice D. Smith, Chen Wang, Bin Cai, Bengang Xu, Lauren Connolly, Ioannis Kramvis, Mustafa Sahin, Zhigang He

 

Science 322, 963-966 (2008)

 

Speaker: Ya-Hsin Hsiao (蕭雅心)

Commentator: Dr. Jung-Yu Hsu(許鍾瑜)

Time: 2009/05/08  15:10~16:00

Place: Room 602

 

Abstract

Damage to the central nervous system (CNS) often results in a permanent loss of function because the injured axons fail to regenerate, which becomes a major obstacle for functional recovery. Many studies on neuronal regeneration have focused on changes in the extracellular environment that inhibits axonal regrowth. However, neutralization of the inhibitory extracellular molecules only leads to limited axon regeneration in vivo. Here, the authors took a novel approach to examine genes and their associated molecular pathways that promote neuronal growth during normal development but are suppressed in adult neurons. They hypothesized that down-regulation of these growth-related genes and subsequent protein synthesis contributes to an overall inability to re-activate growth programs that would be needed for axonal regeneration in adults. They chose mouse optic nerve as a research model and analyzed cell growth control genes using a virus-assisted in vivo conditional knockout approach. They found that deletion of PTEN (phosphatase and tensin homolog), a negative regulator of the mTOR (mammalian target of rapamycin) pathway, in adult retinal ganglion cells (RGCs) promoted robust axon regeneration after optic nerve injury. Axon injury suppressed the mTOR pathway and subsequent protein synthesis in adult RGCs. Similarly, re-activating this mTOR pathway by conditional knockout of tuberous sclerosis complex 1 (TSC1), another negative regulator of the mTOR pathway, was sufficient to promote axon regeneration. Their studies demonstrated that re-activating intrinsic growth permissive pathways is critical for axon regeneration after CNS injuries in adults and is a promising therapeutic approach in the future.

 

References:

1. G. Yiu, Z. He, Nat. Rev. Neurosci. 7, 617 (2006).

2. N. Y. Harel, S. M. Strittmatter, Nat. Rev. Neurosci. 7, 603 (2006).