A research team at the University of California, Irvine is the first to reveal that a molecule in the brain, ophthalmic acid, unexpectedly acts as a dopamine-like neurotransmitter in regulating motor function, offering a new therapeutic target for Parkinson’s and other movement disorders. diseases.
In the study, published in the October issue of the journal BrainThe researchers observed that ophthalmic acid binds to and activates calcium-sensing receptors in the brain, reversing movement deficiencies in mouse models of Parkinson’s for more than 20 hours.
The disabling neurogenerative disease affects millions of people worldwide over the age of 50. The symptoms, which include tremors, tremors, and lack of movement, are caused by decreased dopamine levels in the brain as those neurons die. L-dopa, a first-line drug for treatment, acts by replacing lost dopamine and lasts two to three hours. While initially successful, the effect of L-dopa fades over time and its prolonged use leads to dyskinesia (erratic, involuntary muscle movements in the patient’s face, arms, legs, and torso).
“Our findings present a groundbreaking discovery that potentially opens a new door in neuroscience by challenging the more than 60-year-old view that dopamine is the exclusive neurotransmitter in the control of motor function,” said co-author Amal Alachkar, of the School of Professor of Pharmacy and Pharmaceutical Sciences. “Surprisingly, ophthalmic acid not only enabled movement, but also far outperformed L-dopa in maintaining positive effects. Identification of the ophthalmic acid calcium-sensing receptor pathway, a previously unrecognized system, opens promising new avenues for movement disorder research and therapeutic interventions, especially for patients with Parkinson’s disease.”
Alachkar began his research into the complexities of motor function beyond the limits of dopamine more than two decades ago, when he observed robust motor activity in dopamine-depleted mouse models of Parkinson’s. In this study, the team performed extensive metabolic examinations of hundreds of brain molecules to identify which ones are associated with motor activity in the absence of dopamine. After exhaustive behavioral, biochemical and pharmacological analyses, ophthalmic acid was confirmed to be an alternative neurotransmitter.
“One of the critical obstacles in the treatment of Parkinson’s is the inability of neurotransmitters to cross the blood-brain barrier, which is why L-DOPA is given to patients to convert it into dopamine in the brain,” Alachkar said. “We are now developing products that release ophthalmic acid into the brain or enhance the brain’s ability to synthesize it while we continue to explore the full neurological function of this molecule.”
Team members also included doctoral student and lab assistant Sammy Alhassen, who is now a postdoctoral fellow at UCLA; laboratory specialist Derk Hogenkamp; project scientist Hung Anh Nguyen; PhD student Saeed Al Masri; and co-corresponding author Olivier Civelli, Eric L. and Lila D. Nelson Professor of Neuropharmacology, all in the School of Pharmacy and Pharmaceutical Sciences, as well as Geoffrey Abbott, professor of physiology and biophysics and vice dean of basic sciences. research at the Faculty of Medicine.
The study was supported by a grant from the National Institute of Neurological Disorders and Stroke under award number NS107671 and the Eric L. and Lila D. Nelson Chair in Neuropharmacology.
Alachkar and Civelli are inventors on a provisional patent covering products related to ophthalmology and calcium-sensing receptors in motor function.