USE OF SUIF PROTEINS AND HEPARAN SULFATE IN GDNF-DEPENDENT NEURAL INNERVATION AND PROTECTION

摘要

The present invention is based on the discovery that Sulf protein deficiencies lead to direct defects in GDNF-dependent neural innervation and fornnation of neural crest derived enteric glial cells. Sulfs regulate cellular Heparan Sulfate (HS) 6-O-sulfation, and thus reduce GDNF binding to HS, thereby enhancing GDNF signaling to induce neurite outgrowth for muscle innervation. Methods, including Parkinson's Disease, brain injury, and esophageal disorders. Included are methods wherein the increase in GDNF signaling is assayed by monitoring phosphorylation of downstream kinases and formation of glial cells.