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Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro.

Abstract：

:Elevation of cAMP can overcome myelin inhibitors to encourage regeneration of the CNS. We show that a consequence of elevated cAMP is the synthesis of polyamines, resulting from an up-regulation of Arginase I, a key enzyme in their synthesis. Inhibiting polyamine synthesis blocks the cAMP effect on regeneration. Either over-expression of Arginase I or exogenous polyamines can overcome inhibition by MAG and by myelin in general. While MAG/myelin support the growth of young DRG neurons, they become inhibitory as DRGs mature. Endogenous Arginase I levels are high in young DRGs but drop spontaneously at an age that coincides with the switch from promotion to inhibition by MAG/myelin. Over-expressing Arginase I in maturing DRGs blocks that switch. Arginase I and polyamines are more specific targets than cAMP for intervention to encourage regeneration after CNS injury.

journal_name

Neuron

journal_title

Neuron

authors

Cai D,Deng K,Mellado W,Lee J,Ratan RR,Filbin MT

doi

10.1016/s0896-6273(02)00826-7

subject

Has Abstract

pub_date

2002-08-15 00:00:00

pages

711-9

issue

4

eissn

0896-6273

issn

1097-4199

pii

S0896627302008267

journal_volume

35

pub_type

杂志文章

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