Although
Parkinson's disease was first diagnosed nearly 200 years ago, its effective treatment still remains elusive for most of those diagnosed. The gold standard of treatment for most patients is 3,4-dihydroxy-L-phenylalanine. This
drug works for most individuals early in the disease; however, resistant symptoms start to emerge after several years of treatment. There has been increased interest in finding novel
therapies to help
Parkinson's disease patients. Such strategies may have the benefit of not only treating the symptomatic issues of the disorder, but might also offer promise in protecting dopaminergic neurons from further degeneration. One such target that is now receiving much attention from the scientific community is the
metabotropic glutamate receptor mGluR4. In this article, we briefly review
Parkinson's disease and then recent work in the mGluR area, with a focus on the efforts being made toward finding and optimizing novel
mGluR4 positive allosteric modulators (PAMs). Preclinically in rodent models,
mGluR4 activation has offered much promise as a novel treatment of
Parkinson's disease. Additionally, the specific use of PAMs, rather than direct-acting agonists at the orthosteric
glutamate site, continues to be validated as a viable treatment option for this target. It is anticipated that continued progress in this area will further our understanding of the potential of
mGluR4 modulation as a novel symptomatic and potentially disease-modifying treatment for
Parkinson's disease.