Modulatory Effects of Ginkgo biloba Against Amyloid Aggregation Through Induction of Heat Shock Proteins in Aluminium Induced Neurotoxicity.

Abstract

Protein misfolding and aggregation of amyloid beta (Aβ) peptide, as well as formation of neurofibrillary tangles (NFTs) are the signature hallmarks of Alzheimer's disease (AD) pathology. To prevent this, molecular chaperones come into play as they facilitate the refolding of the misfolded proteins and cell protection under stress. Here, we have evaluated the possible effects of Ginkgo biloba (GBE) against aggregation of the Aβ through activation of heat shock proteins (HSPs) in the Aluminium (Al) induced AD based model. GBE (100 mg/kg body weight) was administered per oral to the female SD rats in conjunction with intraperitoneal (i.p.) injection of Al lactate (10 mg/kg body weight) for six weeks. Pretreated animals were administered GBE for additional two weeks prior to any exposure of Al. GBE administration resulted in decrease in Aβ aggregation, ubiquitin deposition, accompanying a significant decline in APP & Tau protein hyperphosphorylation which can be attributed to activation of Heat shock factor (HSF-1) and upregulation in the protein expression of HSPs. Histopathological investigation studies have also shown the decrease in aggregation of Aβ peptide by GBE administration. Additionally, the decrease in ROS levels and Aβ aggregation by GBE administration prohibited the decline in the neurotransmitter levels and monoamine oxidase levels in hippocampus and cortex. This further caused improvement in learning and memory of the animals. In conclusion, our results indicate that GBE prevents the symptoms of Al induced AD like pathophysiology by upregulating the HSPs levels and decreasing the aggregation load.

• Authors: Sonia Verma, Sheetal Sharma, Pavitra Ranawat, Bimla Nehru
• Journal: Neurochemical research (Neurochem Res) Vol. 45 Issue 2 Pg. 465-490 (Feb 2020) ISSN: 1573-6903 [Electronic] United States
• PMID: 31894463 (Publication Type: Journal Article)

Chemical References

• Amyloid beta-Peptides
• Heat-Shock Proteins
• Mapt protein, rat
• Neuroprotective Agents
• Plant Extracts
• Reactive Oxygen Species
• tau Proteins
• Ginkgo biloba extract
• Serotonin
• Aluminum
• Monoamine Oxidase
• Acetylcholinesterase
• Epinephrine

Topics

• Acetylcholinesterase (metabolism)
• Aluminum (toxicity)
• Amyloid beta-Peptides (metabolism)
• Animals
• Dentate Gyrus (pathology)
• Epinephrine (metabolism)
• Female
• Ginkgo biloba (chemistry)
• Heat-Shock Proteins (metabolism)
• Maze Learning (drug effects)
• Monoamine Oxidase (metabolism)
• Neuroprotective Agents (therapeutic use)
• Neurotoxicity Syndromes (drug therapy, pathology)
• Plant Extracts (therapeutic use)
• Protein Multimerization (drug effects)
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Serotonin (metabolism)
• tau Proteins (metabolism)