Life Sciences & Biotechnology
Title : | Molecular mechanistic role of ar- turmerone, a promising drug candidate for the treatment of Parkinson’s disease. |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. BerylVedha Yesudhason, Sathyabama Institute Of Science And Technology (Deemed To Be University), Tamil Nadu |
Timeline Start Year : | 2022 |
Timeline End Year : | 2025 |
Contact info : | berylbiotech@yahoo.com |
Equipments : | Multiplate reader |
Details
Executive Summary : | Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by progressive motor symptoms, such as bradykinesia, resting tremor, and rigidity. Dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the midbrain selectively and progressively degenerate in patients affected with PD. In response to any kind of brain damage or injury, microglia cells activated and produce neuro-inflammatory factors such as cytokines, chemokines and nitric oxide, which leads to inflammation-mediated neuronal cell death and brain injury. Repairing ability of the neural stem cells (NSCs) was prevented by microglia. Activated microglia interacts with NSCs and thereby retards their respective functions. Because of this interaction, microglia leads expansion of lesion cavity which further results in brain damage. Once the activation of microglia is blocked, NSCs can self-repair the damaged brain. Interestingly, a bioactive compound namely aromatic (ar)-turmerone (a phytochemical) from Curcuma longa blocks the key signaling pathways in microglia. Ar-turmerone has the ability to cross the blood brain barrier and activate NSCs in the brain but the molecular mechanism remains unknown. In addition, ar-turmerone protect the dopaminergic neurons in an independent way by activating Nrf2 without inhibiting the microglial activation. Preliminary work done by the PI recently reported the toxicology of ar-turmerone on zebrafish embryos by checking the lethal endpoints such as coagulation, lack of somite formation, non‐detachment of tail, and lack of heartbeat. All the above lethality was not observed after ar-turmerone treatment and the LC50 was found to be 144 μg. In addition, unpublished results show that ar-turmerone has the ability to rescue the cells from apoptosis. Studies with Sox2 antibodies clearly indicate that ar-turmerone has the ability to induce proliferating stem cells. Molecular docking of ar-turmerone with Keap-Nrf2 protein, shows the binding affinity of -7.33. This finding suggests that ar-turmerone play a key role in the recovery of dopaminergic neurons in PD. Hence it is necessary to find out the molecular mechanism underlying. For executing this work, Parkinson zebrafish and rat model that depict the characteristics of the PD more accurately are needed to be developed. This model will be very helpful in identifying; how ar-turmerone specifically binds to the microglia; and the molecular mechanistic role of ar-turmerone on Neural Stem Cell activation. Finally, the mechanism behind the activation of Nrf2 and other factors that binds with ar-turmerone on protecting the dying dopaminergic neurons will be validated. The results obtained from this in vitro model will provide an important step in establishing therapeutic paradigms incorporating ar-turmerone for providing benefit to those suffering from unbearable neurological conditions and it will bring a bloom in the life of people suffering with PD. |
Co-PI: | Dr. JohnsonRetnarajSamuel SelvanChristyraj, Sathyabama Institute Of Science And Technology (Deemed To Be University), Tamil Nadu-600119 |
Total Budget (INR): | 27,13,425 |
Organizations involved