Disorders of the Nervous System
Author: Micaela B. Cuk | Email: micaelacuk@gmail.com
Micaela B. Cuk 1°, Hernán E. Hauché P.1°, Melina Bordone 1°, Juan Ferrario1°
1° Laboratorio de Neurobiología de la Enfermedad de Parkinson (IB3, UBA) Ciudad Autónoma de Buenos Aires, Argentina.
Parkinson’s Disease(PD) is the second most prevalent neurodegenerative disease, characterized by the progressive death of dopaminergic neurons, leading to impaired motor control. Levodopa(L-DOPA) is the gold standard treatment for PD, but its long-term use often results in levodopa-induced dyskinesias(LIDs), which represents a therapeutic challenge itself.
Currently, amantadine(AMN), a NMDA receptor antagonist, is the only available option to reduce LIDs, although it has side effects that limit its use. NMDA-R is a key molecular player in LIDs and thus an attractive therapeutic target.
The aim of this project is to develop an in vitro cellular model of LID by reproducing molecular changes that recapitulates those in vivo. So far, we have settled down treatment conditions in vitro to stimulate NMDA- R (with NMDA as the receptor agonist) and determine the phosphorylation of ERK in combination with AMN as an inhibitor, and saracatinib, an inhibitor of the Fyn kinase and a central player in NMDA receptor activation.Our next step is to reproduce these results in the STHdhQ7/Q7 cell line, a mouse striatal neuron cell line that expresses several markers of direct striatonigral pathway such as D1 receptors, NMDA-R, and several signaling elements previously described in vivo for this neuronal type. We expect that this novel in vitro model will be useful to analyze novel targets for LIDs in a faster and cheaper way and reduce the use of experimental animals.