Summary: A new study has discovered that ocular acid, a protein in the head, acts like a hormone to govern engine function, related to dopamine. In Parkinson’s keyboard designs, this protein improved motion for over 20 hours—far longer than the effects of the current care, L-dopa.
This finding challenges the conventional wisdom that motor power is largely dependent on dopamine alone. Researchers are currently looking into how to use ocular acid as a possible treatment for movement disorders, giving hope to more potent treatments.
Important Facts:
- Ophthalmic acid functions as a hormone to regulate engine performance.
- It improved action for around 20 hours in Parkinson’s mouse models.
- This finding opens up new avenues of treatment for action diseases like Parkinson’s.
Origin: UC Irvine
Quickly acting like a hormone similar to serotonin in regulating engine function, a research team from the University of California, Irvine is the first to discover that a molecule in the brain, ocular acid, offers a new medical target for Parkinson’s and another movement diseases.
In the study, published in the October problem of the journal , Brain, researchers observed that ocular acid binds to and produces calcium-sensing receptor in the head, reversing the action difficulties of Parkinson’s mouse designs for more than 20 hours.
Millions of people over the age of 50 are affected by the incurable neurogenerative disease. Symptoms, which include tremors, shaking and lack of movement, are caused by decreasing levels of dopamine in the brain as those neurons die. L-dopa, the front-line drug for treatment, acts by replacing the lost dopamine and has a duration of two to three hours.
While initially successful, the effect of L-dopa fades over time, and its long-term use leads to dyskinesia – involuntary, erratic muscle movements in the patient’s face, arms, legs and torso.
Our findings provide a ground-breaking insight into neuroscience by challenging the more than 60-year-old notion that dopamine is the sole neurotransmitter in motor function control, according to co-author Amal Alachkar, School of Pharmacy &, professor of Pharmaceutical Sciences.
” Remarkably, ophthalmic acid not only enabled movement, but also far surpassed L-dopa in sustaining positive effects. The identification of the ophthalmic acid-calcium-sensing receptor pathway, a previously unrecognized system, opens up promising new avenues for movement disorder research and therapeutic interventions, especially for Parkinson’s disease patients”.
More than 20 years ago, Alachkar began her investigation into the complex nature of motor function by observing robust motor activity in Parkinson’s mouse models without dopamine.
In this study, the team examined hundreds of brain molecules to find which ones are linked to motor activity in the absence of dopamine. After thorough behavioral, biochemical and pharmacological analyses, ophthalmic acid was confirmed as an alternative neurotransmitter.
” One of the key obstacles in Parkinson’s treatment is the inability of neurotransmitters to cross the blood-brain barrier, which is why L-DOPA is given to patients to be converted into dopamine in the brain,” Alachkar said.
As we continue to study the full range of this molecule’s full neurological function,” We are now developing products that either release ophthalmic acid in the brain or enhance the brain’s ability to synthesize it.”
Additionally, team members included assistant professor and assistant professor Sammy Alhassen, who is currently a postdoctoral scholar at UCLA, lab specialist Derk Hogenkamp, project scientist Hung Anh Nguyen, project scientist Saeed Al Masri, and co-corresponding author Olivier Civelli, who holds the Eric L. and Lila D. Nelson Chair in Neuropharmacology, as well as Geoffrey Abbott, professor of physiology &, biophysics and vice dean of basic
Funding: 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.
A provisional patent that covers products involving ophthalmate and calcium-sensing receptors in motor function was created by Alachkar and Civelli.
About this neuropharmacology and Parkinson’s disease research news
Author: Patricia Harriman
Source: UC Irvine
Contact: Patricia Harriman – UC Irvine
Image: The image is credited to Neuroscience News
Original Research: Closed access.
Amal Alachkar and colleagues ‘” Ophthalmate has a new CaSR-based motor function regulator; implications for movement disorders.” Brain
Abstract
Ophthalmate has a new CaSR-based motor function regulator; implications for movement disorders
Dopamine’s role as the principal neurotransmitter in motor functions has long been accepted. By demonstrating the involvement of non-dopaminergic mechanisms, we extend this conventional perspective.
We observed a significant motor response in mouse models of Parkinson’s disease even when the enzyme aromatic amino acid decarboxylase ( AADC ) was blocked from its conversion to dopamine.
Remarkably, the motor activity response to , L-DOPA in the presence of an AADC inhibitor ( NSD1015 ) showed a delayed onset, yet greater intensity and longer duration, peaking at 7 h, compared to when , L-DOPA was administered alone.
This suggests an alternative pathway or mechanism, independent of dopamine signalling, mediating the motor functions.
We used comprehensive metabolomics analysis to identify the metabolites that are linked to the pronounced hyperactivity observed.
Our findings demonstrated that the tripeptide ophthalmic acid ( also known as ophthalmate in its anionic form )’s peak in motor activity in Parkinson’s disease mice is related to a 20-fold increase in brain levels.
Interestingly, we found that administering ophthalmate directly to the brain rescued motor deficits in Parkinson’s disease mice in a dose-dependent manner.
We investigated the molecular mechanisms underlying ophthalmate’s action and discovered, through radioligand binding and cAMP-luminescence assays, that ophthalmate binds to and activates the calcium-sensing receptor ( CaSR ).
Additionally, our findings confirmed that ophthalmate’s motor-enhancing effects are inhibited by a CaSR antagonist, further supporting the idea that CaSR activation controls motor functions.
The use of ophthalmate as a novel motor function regulator has the potential to significantly advance our understanding of brain mechanisms controlling movement and the treatment of related disorders.
