| First Author | Hedstrom KL | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 6 | Pages | 2325-30 |
| PubMed ID | 24449858 | Mgi Jnum | J:206435 |
| Mgi Id | MGI:5550287 | Doi | 10.1073/pnas.1308889111 |
| Citation | Hedstrom KL, et al. (2014) Treating small fiber neuropathy by topical application of a small molecule modulator of ligand-induced GFRalpha/RET receptor signaling. Proc Natl Acad Sci U S A 111(6):2325-30 |
| abstractText | Small-fiber neuropathy (SFN) is a disorder of peripheral nerves commonly found in patients with diabetes mellitus, HIV infection, and those receiving chemotherapy. The complexity of disease etiology has led to a scarcity of effective treatments. Using two models of progressive SFN, we show that overexpression of glial cell line-derived neurotrophic factor (GDNF) in skin keratinocytes or topical application of XIB4035, a reported nonpeptidyl agonist of GDNF receptor alpha1 (GFRalpha1), are effective treatments for SFN. We also demonstrate that XIB4035 is not a GFRalpha1 agonist, but rather it enhances GFRalpha family receptor signaling in conjunction with ligand stimulation. Taken together, our results indicate that topical application of GFRalpha/RET receptor signaling modulators may be a unique therapy for SFN, and we have identified XIB4035 as a candidate therapeutic agent. |
