Dopamine’s role as the principal neurotransmitter in motor functions has long been accepted. A new study now demonstrates the involvement of non-dopaminergic mechanisms.
The study by the University of California, Irvine, is the first to reveal that a molecule in the brain – ophthalmic acid – unexpectedly acts like a neurotransmitter similar to dopamine in regulating motor function.
The team observed that ophthalmic acid binds to and turns on calcium-sensing receptors in the brain. Thus, it reverses the movement impairments of Parkinson’s mouse models for more than 20 hours.
Parkinson’s- a neurogenerative disease, is caused by decreasing levels of dopamine in the brain as those neurons die. L-dopa is the primary medication for treating conditions like Parkinson’s disease by replenishing lost dopamine. Its effects last two to three hours but diminish over time. Long-term use can result in dyskinesia, characterized by involuntary and erratic movements in various body parts.
This groundbreaking discovery opens a new field in neuroscience by challenging the more-than-60-year-old view that dopamine is the exclusive neurotransmitter controlling motor function. Ophthalmic acid has shown impressive potential, facilitating movement and significantly outperforming L-dopa in maintaining positive effects.
The discovery of the ophthalmic acid-calcium-sensing receptor pathway, a previously unknown system, presents exciting new opportunities for research and treatment of movement disorders, particularly those with Parkinson’s.
More than twenty years ago, Amal Alachkar, a School of Pharmacy & Pharmaceutical Sciences professor, began exploring motor function beyond dopamine after noticing significant motor activity in Parkinson‘s mouse models lacking dopamine. Her team conducted extensive metabolic analyses of hundreds of brain molecules to identify those linked to motor activity without dopamine.
They identified ophthalmic acid as an alternative neurotransmitter through detailed behavioral, biochemical, and pharmacological studies.
Alachkar said, “One of the critical hurdles in Parkinson’s treatment is the inability of neurotransmitters to cross the blood-brain barrier, which is why L-DOPA is administered to patients to be converted to dopamine in the brain.”
“We are now developing products that either release ophthalmic acid in the brain or enhance the brain’s ability to synthesize it as we continue to explore the full neurological function of this molecule.”
Journal Reference:
- Sammy Alhassen, Derk Hogenkamp, Hung Anh Nguyen, Saeed Al Masri, Geoffrey W Abbott, Olivier Civelli, Amal Alachkar. Ophthalmate is a new regulator of motor functions via CaSR: implications for movement disorders. Brain. DOI: 10.1093/brain/awae097