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.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2008
Accession Number
ADA481810

Entities

People

  • Li Niu

Organizations

  • State University of New York at Albany

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biochemistry
  • Brain
  • Cell Membrane
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Crystal Structure
  • Gene Expression
  • Medical Personnel
  • Molecular Biology
  • Neurodegeneration
  • Organic Chemistry

Fields of Study

  • Chemistry

Readers

  • Molecular Genetics
  • Molecular and Cellular Biochemistry
  • Neuroscience

Technology Areas

  • Biotechnology