Implications of a Newly Discovered DR5 Specific Antagonistic Peptide for Neurodegenerative Disorders

Most neurodegenerative disorders are the result of inflammation and neuronal cell death. Although many cytokines have been implied to be involved in the pathogenesis, recent studies have shown TRAIL to be responsible for neuronal apoptosis. TRAIL is best known for its ability to induce apoptosis in many cancer cells. Normally TRAIL is not present in the CNS. However, it is induced by β‐amyloid protein and upregulated on infected macrophages which can infiltrate the CNS. TRAIL is able to induce apoptosis via death receptors DR4 and DR5. DR5 is shown to be expressed on neuronal cells. The identification of an antagonistic peptide that specifically binds DR5 provides us with a useful investigative tool. Small peptides can bind their targets with high affinity and specificity. In addition, they are easily modified and further developed for clinical application. So the peptide R2C16 might even be used as a lead peptide for the development of therapeutic agents in neurodegenerative disorders.