for treating mental disorders
Yale research on the new protein Calcyon could lead to development of more effective drugs for conditions which are marked by dopamine deficiency, such as Parkinson's, chronic schizophrenia and possibly attention deficit hyperactivity disorder.
Researchers at Yale and the Medical College of Georgia have identified proteins in the dopamine signaling pathway, which interact with the D1 receptor, one of five known dopamine receptors. In the March 3 issue of Science, they describe how a novel protein called Calcyon (for calcium "on") interacts with the D1 receptor to enhance release of calcium within the cell, thereby increasing dopamine's actions.
"The D1 receptor is prominent in prefrontal cortical neurons that carry out memory functions and we found that Calcyon is also present in the same cells," explains Patricia Goldman-Rakic, professor of neurobiology, neurology and psychiatry at the School of Medicine. "The next step is to learn if Calcyon can increase the response of these neurons in the living animal."
This work, Goldman-Rakic says, reveals a new pathway for D1 signaling and it opens up the possibility that Calcyon may be a new target for drug development aimed at improving the signaling in cells which are otherwise desensitized to dopamine. This is particularly important, she notes, because most of the drugs now used in those disorders have negative consequences after long-term use.
The team's studies have now shown that memory impairments produced by loss of D1 stimulation can be reversed by the application of an experimental drug which stimulates the D1 receptor specifically.
"We've seen only positive results in laboratory trials," Goldman-Rakic says. "The time is right for clinical trials with drugs containing D1 agonist properties."
The research is the result of a long-term collaboration between Yale investigators and Clare Bergson and Robert Levenson, under the sponsorship of the Center for Neuroscience of Mental Disorders directed by Goldman-Rakic. Bergson and Levenson, formerly at Yale, are now in the department of pharmacology and toxicology at the Medical College of Georgia, and at the Pennsylvania State College of Medicine, respectively.
-- By Karen Peart
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