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

Jeffrey Chang
Sep 16, 2011
Fall 2011,
N58 RNA pool, p75NGFR

Here is my proposal link

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

I also updated my abstract so I am reposting it.

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.