Jeffrey Chang jc49767
When a traumatic injury occurs to the central nervous system, or CNS, the axons of the affected cells are damaged and unable to conduct electrical signals vital to cell communication. These cells are unable to regenerate largely due to the inhibitory property of central myelin (Xie, Zheng, 2007). There are three main myelin-derived inhibitors, Nogo, MAG, and OMgp, which “bind with high affinity to the Nogo-66 receptor (NGR) on axons and limit neurite outgrowth (Wang et al, 2010).” When one of these three inhibitors binds to NGR, it forms a receptor complex with a transmembrane co-receptor known as p75NTR (neurotrophin receptor) to transduce the inhibitory signal (Wang et al, 2010). If p75NTR does not function properly in a neuron, the signal inhibiting axon regeneration will not effectively be transduced because p75NTR is a major, but not exclusive, co-receptor of NGR (Xie, Zhen, 2007).
Aptamers, or specific nucleic acid species, can be selected against a target, which in this case is p75NTR, in hopes that a specific species will have a high binding affinity for the target. Aptamer technology is cutting-edge since it is capable of discriminating between related targets by a single amino acid or functional group. A few of the possible applications of aptamer technology include drug delivery, therapeutics, detection, and in vivo diagnostic imaging. If an aptamer is developed which selects against p75NTR, the axons of damaged neurons will be able to begin repairing themselves.
Specific Aim 1: RNA Aptamer Selection against p75NTR for therapeutic treatment
In order to transduce an inhibitory signal, NGR utilizes p75NTR as a main co-receptor. If successful aptamer selection against p75NTR occurs, NGR will not be able to effectively communicate its inhibitory signal, therefore allowing the beginnings of axon regeneration. Selection against NGR has already been undergone, but by also selecting against p75NTR, the chance of any inhibitory signal being transduced drastically decreases. This aptamer can be used therapeutically in the recovery of patients with central nervous system damage.
Figure 1: Schematic Diagram of Steps Leading to Inhibitory Response of Axon Regeneration: An aptamer selected against p75NTR will prevent a signal transduction pathway.
Traumatic injuries involving the CNS are extremely difficult to aid and there are no successful treatments targeting the source of the problem. By preventing the major inhibitory roles of myelin with the selection of nucleic acid aptamers against p75NTR, the axons of damaged neurons will undergo the beginning stages of repair. The success of this research may further support the idea that aptamer selection against major inhibitors of axon regeneration can lead to the effective treatment of patients with CNS injuries.
P75NTR can be purchased from abcam at 15 µg for $325.00. The catalog number is ab83679. http://www.abcam.com/p75-ngf-receptor-protein-fc-chimera-ab83679.html
1. Xie, Fang and Zheng, Binhai. "White matter inhibitors in CNS axon regeneration failure." Exp Neurol 209.2 (2007): 302-312. Web. 29 Aug 2011.
2. Wang, Yuxuan, Zin Khaing, Na Li, Brad Hall, and Christine Schmidt. "Aptamer Antagonists of Myelin-Derived Inhibitors Promote Axon Growth." PLoS One 5.3 (2010): n. pag. Web. 29 Aug 2011.