Evaluation of contribution of GSK-3 in 6-OHDA model in Parkinson's Disease

• Grant number: 18/13015-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2018
• End date: August 31, 2020
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Luiz Roberto Giorgetti de Britto
• Grantee: Ana Flavia Tostes da Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder that affects the central nervous system, which can manifest itself genetically or sporadically. The main finding of this disorder is the death of dopamine producing neurons in the substantia nigra causing the characteristic symptoms of the disease; bradykinesia, rigidity, rest tremor and postural instability. Previous studies mention that during apoptosis of dopaminergic neurons, an enzyme GSK-3² increases in its active form, being an enzyme involved in innumerable cell signaling pathways. With the increase in the production of reactive oxygen species (ROS) from inhibition of the mitochondrial complex I or by other reactions that release ROS, the enzyme GSK-3² is activated by the Akt pathway, a fact that will promote inhibition of serine phosphorylation 9 (inactive form) and activation of tyrosine 216 phosphorylation (active form) in this enzyme. 6-OHDA is a neurotoxin that promotes neuronal death in Parkinsonian models induced by the aministration of this substance and from that it is suggested that its mechanismo faction acts producing ROS, having a correlation with the activation of GSK-3² in the active form. The use of a specific GSK-3² inhibitor such as lithium may report the influence of the contribution of GSK-3² enzyme on 6- OHDA modelsandis a possible explanation of the neuroprotective action of lithium and in the future can be seen as a pharmacological therapy directed to DP.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Ana Flavia Tostes da. Effect of lithium chloride in 6-OHDA Parkinsons Disease model.. 2021. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.