Nucleic Acid Aptamer Selection Against p75NGFR for the Promotion of Axon Regeneration in Central Nervous System Injuries

Jeffrey Chang

When I posted my new abstract along with my proposal, it messed up my picture so I am just reposting my abstract:

Here is a link to my final manuscript: http://dl.dropbox.com/u/42010369/Chang_Jeffrey%20-%20Final%20Manuscript%20Nucleic%20Acid%20Aptamer%20Selection%20Against%20p75NGFR%20for%20the%20Promotion%20of%20Axon%20Regeneration%20in%20Central%20Nervous%20System%20Injuries.docx

Here is a link to my proposal: http://dl.dropbox.com/u/42010369/Chang_Jeffrey%20-%20Target%20Proposal%20Nucleic%20Acid%20Aptamer%20Selection%20Against%20p75NGFR%20for%20the%20Promotion%20of%20Axon%20Regeneration%20in%20Central%20Nervous%20System%20Injuries.docx

Abstract:

Damaged axons resulting from central nervous system (CNS) injuries are 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). When one of the three main myelin-derived inhibitors binds to NGR (Nogo-66 receptor), NGR forms a receptor complex with a transmembrane co-receptor protein known as p75NGFR (nerve growth factor receptor) to transduce the inhibitory signal (Wang et. Al, 2010).

Aptamers, or specific nucleic acid species, are selected against a target in hopes that a specific species would have a high binding affinity for the target. A few of the possible applications of aptamer technology include drug delivery and therapeutics. An aptamer developed to select against p75NGFR would enable the axons of damaged neurons to begin regeneration.

Specific Aim 1: RNA Aptamer Selection against p75NGFR for therapeutic treatment

The inhibitory effect of central myelin on the regeneration of damaged axons causes central nervous system injuries to be permanent. If an aptamer was able to successfully select against p75NGFR by preventing NGR from binding to p75NGFR, NGR would not be able to effectively communicate its inhibitory signal, therefore allowing the beginnings of axon regeneration as shown in Figure 1. This aptamer would 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 p75NGFR prevents a signal transduction pathway. Without this pathway, an inhibitory response would not occur and axons would begin regeneration.

P75NGFR can be purchased from Novus Biologicals at 25 µg for $460.00. The catalog number is H00004804-Q01 and the website is http://www.novusbio.com/p75-NGF-Receptor-Partial-Recombinant-Protein_H00004804-Q01.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. .