The Michael Stern Parkinson’s Research Foundation funds five world renowned doctors researching PD.
Our scientists are at the forefront of research and, based on their understanding of how the disease ravages the brain, have developed many insights into how the devastating symptoms of Parkinson’s disease might be prevented or delayed.
We have selected recent samples of scientific studies from major publications such as Nature, Science and the Proceedings of the National Academy of Sciences (PNAS). Listed below you will find a synopsis of each of the studies provided, and you will have the option to view a full description and to download the original version if you so desire.
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Parkinson’s disease (PD) is characterized by a progressive degeneration of substantia nigra dopaminergic neurons projecting to the striatum. Restoration of dopamine transmission by L-DOPA relieves symptoms of PD but causes prominent side effects. There is a strong serotonin innervation of the striatum by serotonergic neurons that remains relatively preserved in PD. The study of this innervation has been largely neglected. Here, we demonstrate that chronic L-DOPA administration to 6-OHDA-lesioned rodents increases, via D1 receptors, the levels of the 5-HT1B receptor and its adaptor protein, p11, in dopamine-denervated striatonigral neurons. Using unilaterally 6-OHDA-lesioned p11 WT and KO mice, it was found that administration of a selective 5-HT1B receptor agonist, CP94253, inhibited L-DOPA-induced rotational behavior and abnormal involuntary movements in a p11-dependent manner. These data reveal an L-DOPA-induced negative-feedback mechanism, whereby the serotonin system may influence the symptomatology of Parkinsonism.
DARPP-32 is protein found in the part of the brain responsible for dopamine signaling. This part of the brain is damaged in Parkinson’s disease. DARPP-32 controls how specific brain cells react to the neurotransmitter, dopamine. Therefore, DARPP-32 is essential for normal brain function, especially where movement is concerned. Scientists at The Michael Stern Parkinson’s Research Foundation at The Rockefeller University have discovered much about how DARPP-32 functions. They have learned that it regulates the functioning of other proteins and is, itself, regulated by a protein called PP-1, which in turn regulates many other proteins in brain cells and is also critically important for normal function.Stern scientists discovered that PP-1 and DARPP-32 not only regulate each other, but that they do so by binding to one another in a very specific way. Discovery of this site of binding is expected to allow scientists to design drugs that will alter how the two proteins bind together and thus affect how DARRP-32 functions conditions such as Parkinson’s disease.