Functional inhibition of the p75 receptor using a small interfering RNA.
The neurotrophin receptor p75(NTR) mediates a wide variety of biological effects. Consistent with the function in controlling the survival and neurite formation, p75(NTR) is expressed during the developmental stages of the nervous system. Importantly, p75(NTR) is re-expressed in various pathological conditions and is suggested to contribute to the inhibition of neuronal regeneration and the death of the neurons. Here we develop a tool to knock down the expression of p75(NTR) by employing a small interfering RNA (siRNA). The siRNA for p75(NTR) effectively reduces the expression of endogenous p75(NTR) both in Schwann cells and dorsal root ganglion neurons in vitro. NGF-induced cell death in Schwann cells and the neurite retraction in DRG neurons induced by myelin-associated glycoprotein are attenuated by the siRNA. Inhibition of p75(NTR) in specific pathological conditions by the siRNA may provide a potential therapeutic agent.
Higuchi
Haruhisa
H
Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Japan.
Yamashita
Toshihide
T
Yoshikawa
Hideki
H
Tohyama
Masaya
M
D000818:Animals; D001483:Base Sequence; D016923:Cell Death; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology; D051379:Mice; D018992:Myelin-Associated Glycoprotein / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics*; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics*; D012583:Schwann Cells / Q000166:cytology
D018992:Myelin-Associated Glycoprotein; D034741:RNA, Small Interfering; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor