PUBLICATION
Hesperidin downregulates kinases lrrk2 and gsk3β in a 6-OHDA induced Parkinson's disease model
- Authors
- Kesh, S., Kannan, R.R., Sivaji, K., Balakrishnan, A.
- ID
- ZDB-PUB-201021-3
- Date
- 2020
- Source
- Neuroscience letters 740: 135426 (Journal)
- Registered Authors
- Keywords
- 6-OHDA, Parkinson's disease, behavior, hesperidin, kinase, zebrafish
- MeSH Terms
-
- Animals
- Antiparkinson Agents/therapeutic use*
- Caspases/metabolism
- Cell Line
- Gene Expression Regulation/drug effects
- Glycogen Synthase Kinase 3/biosynthesis*
- Hesperidin/therapeutic use*
- Hydroxydopamines
- Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/biosynthesis*
- Locomotion/drug effects
- Membrane Potential, Mitochondrial/drug effects
- Neuroprotective Agents/therapeutic use*
- Oxidative Stress/drug effects
- Parkinson Disease, Secondary/chemically induced
- Parkinson Disease, Secondary/drug therapy*
- Parkinson Disease, Secondary/enzymology
- Zebrafish
- Zebrafish Proteins/biosynthesis*
- PubMed
- 33075420 Full text @ Neurosci. Lett.
Citation
Kesh, S., Kannan, R.R., Sivaji, K., Balakrishnan, A. (2020) Hesperidin downregulates kinases lrrk2 and gsk3β in a 6-OHDA induced Parkinson's disease model. Neuroscience letters. 740:135426.
Abstract
The depletion of dopamine in the striatum region and Lewy bodies are the hallmark characteristics of Parkinson's disease. The pathology also includes the upregulation of various Parkinson's disease (PARK) genes and kinases. Two such kinases, LRRK2 and GSK-3β have been directly implicated in the formation of tau and alpha-synuclein proteins, causing PD. Hesperidin (HES) is a flavanone glycoside that has multiple therapeutic benefits including neuroprotective effects. In this study, we examined the neuroprotective effects of HES against 6-hydroxydopamine (6-OHDA) induced-neurotoxicity in the in-vitro and in-vivo model. Hesperidin significantly protected the SH-SY5Y cells' stress against 6-OHDA induced toxicity by downregulating biomarkers of oxidative stress. Furthermore, HES downregulated the kinases lrrk2 and gsk3β along with casp3, casp9, and polg in the zebrafish model. The treatment with HES also improved the locomotor pattern of zebrafish that was affected by 6-OHDA. This study suggests that hesperidin could be a drug of choice in targeting kinases against a 6-OHDA model of PD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping