PUBLICATION
Garcinol pacifies acrylamide induced cognitive impairments, neuroinflammation and neuronal apoptosis by modulating GSK signaling and activation of pCREB by regulating cathepsin B in the brain of zebrafish larvae
- Authors
- Sharma, C., Kang, S.C.
- ID
- ZDB-PUB-200403-28
- Date
- 2020
- Source
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 138: 111246 (Journal)
- Registered Authors
- Keywords
- APP, Acrylamide, Cathepsin-B, Garcinol, Neuro-inflammation, Tau
- MeSH Terms
-
- Acrylamide/adverse effects*
- Animals
- Apoptosis/drug effects*
- Behavior, Animal
- Brain/metabolism*
- Cathepsin B/metabolism*
- Cognitive Dysfunction/chemically induced*
- Disease Models, Animal
- Inflammation/chemically induced*
- Larva/drug effects
- Larva/metabolism
- Mitochondria/drug effects
- Molecular Docking Simulation
- Molecular Dynamics Simulation
- Nerve Tissue Proteins/metabolism
- Neurons/drug effects*
- Terpenes/adverse effects*
- Zebrafish
- PubMed
- 32156567 Full text @ Food Chem. Toxicol.
Citation
Sharma, C., Kang, S.C. (2020) Garcinol pacifies acrylamide induced cognitive impairments, neuroinflammation and neuronal apoptosis by modulating GSK signaling and activation of pCREB by regulating cathepsin B in the brain of zebrafish larvae. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 138:111246.
Abstract
The presence of acrylamide (ACR) in food results in evident cognitive decline, accumulation of misfolded proteins, neurotoxicity, neuroinflammation, and neuronal apoptosis leading to progressive neurodegeneration. Here, we used 4 dpf zebrafish larvae exposed to ACR (1mM/3days) as our model, and neuronal proteins were analyzed. Next, we tested the effect of garcinol (GAR), a natural histone-acetylation inhibitor, whose neuroprotection mechanism of action remains to be fully elucidated. Our result revealed that ACR exposure significantly impaired cognitive behavior, downregulated oxidative repair machinery, and enhanced microglia-induced neuronal apoptosis. Moreover, ACR mediated cathepsin-B (CAT-B) translocation acted as the intracellular secretase for the processing of amyloid precursor protein (APP) and served as an additional risk factor for tau hyper-phosphorylation. Here, GAR suppresses ACR mediated CATB translocation as similar with standard inhibitor CA-074. And, this pharmacological repression helped in inhibiting amyloidogenic APP processing and downstream tau hyper-phosphorylation. GAR neuroprotection was accompanied by CREB, ATF1, and BDNF activation promoting neuronal survival. At the same time, GAR subdued cdk5 and GSK3β, the link between APP processing and tau hyper-phosphorylation. Taken together, our findings indicate that GAR rescued from ACR mediated behavioral defects, oxidative injury, neuroinflammation, undesirable APP processing, tau hyper-phosphorylation which in turn found to be CATB dependent.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping