The environment of the CNS is inhibitory to axonal regeneration after injury, in large part due to inhibitors present in myelin, such as myelin associated glycoprotein (MAG). We have shown that elevating cAMP can overcome myelin inhibitors of regeneration both in vitro and in vivo. This cAMP effect is transcription- dependent; suggesting newly synthesized proteins are needed to overcome inhibition. Our lab has identified several genes that are up-regulated in response to cAMP, one of them is Metallothionein I (MT-I). We have preliminary data that MT-I/II can overcome MAG and myelin mediated inhibition in vitro, using several different primary neuronal cultures. More importantly, MT-I/II exerts its effect by simply being added to the neurons in the presence of the inhibitors. This suggests that MT-I/II may be a novel putative therapeutic agent for intervention to encourage regeneration in vivo. We are now poised to first characterize the effects of MT-I/II in vitro and pursue a potential mechanism, which we suspect that MT-I/IJ is blocking the signaling pathway of MAG binding to the NgR-Lingo-p75 receptor complex that mediates this inhibition. We also plan to see if MT-I/II can promote axonal regeneration in an in vivo spinal cord injury model. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS054511-02
Application #
7216325
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Utz, Ursula
Project Start
2006-03-15
Project End
2009-03-14
Budget Start
2007-03-15
Budget End
2008-03-14
Support Year
2
Fiscal Year
2007
Total Cost
$50,428
Indirect Cost
Name
Hunter College
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
620127915
City
New York
State
NY
Country
United States
Zip Code
10065
Siddiq, Mustafa M; Hannila, Sari S; Carmel, Jason B et al. (2015) Metallothionein-I/II Promotes Axonal Regeneration in the Central Nervous System. J Biol Chem 290:16343-56