Microglia activation leads to inflammation mediated dopaminergic degeneration in the brain of patients with Parkinson and Alzheimer's Disease. Thus Identification of drugs that reduce microglia activation could prevent or reverse neuronal degeneration in these diseases and other degenerative CNS disorders.

This invention describes small-peptide and non-peptide molecules that inhibit microglia activation and prevent neuronal degeneration with a bi-modal dose response curve. The non-peptide compounds have also been shown to prevent dopamine neuronal degeneration in animal models. This invention provides compositions and methods for inhibiting inflammatory mechanisms and treating inflammation-related condition by administering ultra-low (femto-molar) doses of at least one compound of the invention. These compounds include morphinans, opioid peptides, and the tripeptide GGF.