Glutamate Receptor Aptamers and ALS
Abstract
Excitotoxicity is one of the leading causes for amyotrophic lateral sclerosis (ALS). Our goal was to develop a novel class of powerful aptamer-based, anti-excitotoxic inhibitors against GluR2Qflip, a key AMPA receptor subunit that controls the calcium permeability and mediates excitotoxicity. An aptamer is a single-stranded nucleic acid that directly inhibits a protein's function by folding into a specific tertiary structure that dictates high-affinity binding to the target protein. To date, we have identified two classes of aptamers (i.e. competitive and noncompetitive aptamers) against GluR2Qflip, by using a molecular biology approach called systematic evolution of ligands by exponential enrichment (SELEX). These aptamers are water soluble and have a nanomolar affinity against GluR2Qflip. Their inhibitory properties rival those of any existing small, chemical inhibitors. We are continuing to work with these aptamers towards developing them into anti-excitotoxic drugs for treating patients with ALS, including those Gulf War veterans suffering from ALS.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2009
- Accession Number
- ADA499664
Entities
People
- Li Niu
Organizations
- State University of New York at Albany