Parkinson Disease: Zoli M

Picciotto MR, Zoli M. · Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA. · Front Biosci. · Pubmed #17981563 No free full text.

Abstract: Epidemiological studies have identified a negative correlation between smoking and the development of neurodegenerative disorders such as Parkinson's disease, and in some studies, Alzheimer's disease. These findings have been attributed to the ability of nicotine to act as a neuroprotective agent. A large number of studies demonstrate that nicotine can protect against neuronal death in vitro and in vivo, and the mechanisms underlying the ability of nicotine to protect against excitotoxicity and amyloid-? toxicity are beginning to be elucidated. Despite the compelling evidence that nicotine is neuroprotective, it is clear that nicotine can be toxic under some circumstances. The balance between nicotine neuroprotection and toxicity depends on dose, developmental stage and regimen of administration. Therefore, a full understanding of the molecular and cellular effects of nicotine on signaling pathways relevant to neuronal survival is critical for informed drug discovery of nicotinic compounds to combat human neurodegeneration. This review summarizes recent studies related to the mechanisms underlying nicotine-mediated neuroprotection, and addresses issues that are relevant to use of nicotine as a neuroprotective agent in vivo.

Hillion J, Canals M, Torvinen M, Casado V, Scott R, Terasmaa A, Hansson A, Watson S, Olah ME, Mallol J, Canela EI, Zoli M, Agnati LF, Ibanez CF, Lluis C, Franco R, Ferre S, Fuxe K. · Department of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden. · J Biol Chem. · Pubmed #11872740 links to  free full text

Abstract: Antagonistic and reciprocal interactions are known to exist between adenosine and dopamine receptors in the striatum. In the present study, double immunofluorescence experiments with confocal laser microscopy showed a high degree of colocalization of adenosine A(2A) receptors (A(2A)R) and dopamine D(2) receptors (D(2)R) in cell membranes of SH-SY5Y human neuroblastoma cells stably transfected with human D(2)R and in cultured striatal cells. A(2A)R/D(2)R heteromeric complexes were demonstrated in coimmunoprecipitation experiments in membrane preparations from D(2)R-transfected SH-SY5Y cells and from mouse fibroblast Ltk(-) cells stably transfected with human D(2)R (long form) and transiently cotransfected with the A(2A)R double-tagged with hemagglutinin. Long term exposure to A(2A)R and D(2)R agonists in D(2)R-cotransfected SH-SY5Y cells resulted in coaggregation, cointernalization and codesensitization of A(2A)R and D(2)R. These results give a molecular basis for adenosine-dopamine antagonism at the membrane level and have implications for treatment of Parkinson's disease and schizophrenia, in which D(2)R are involved.