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

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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.

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Abbreviations

Al:

Aluminium

ROS:

Reactive oxygen species

DCF:

2′7′-Dichlorofluorescceine

Aβ:

Amyloid beta

FTIR:

Fourier transform infrared spectroscopy

HSPs:

Heat shock proteins

AChE:

Acetylcholinesterase

MWM:

Morris water maze

GBE:

Ginkgo biloba extract

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Acknowledgements

We wish to thank Prof. Suresh Kumar of Department of Statistics for their valuable advice and support in analyzing the data.

Funding

The study was carried out by the funds received by University grants commission-Basic Scientific research (UGC-BSR) to Ms Sonia Verma and DST-PURSE 2017–18, New Delhi to Department of Biophysics, Panjab University.

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  1. Department of Biophysics, South Campus, Panjab University, Chandigarh, 160014, India

    Sonia Verma, Sheetal Sharma, Pavitra Ranawat & Bimla Nehru

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SV has carried out all the research work presented in this article. She has analysed all the results of molecular biology and histopathological studies. She has written and edited the scientific article. Prof. BN and Dr. PR has given their valuable advice and support in carrying out this piece of work and in the preparation of this manuscript. Dr. SS has helped the author with his valuable suggestions in the research work and writing the article.

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Correspondence to Bimla Nehru.

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All the protocols performed were approved by Animal Ethical Committee (IAEC) of Panjab University, Chandigarh, India with approval no. PU/45/99/CPCSEA/IAEC/2018/153. Every effort was made to minimize the number of animals and the distress caused throughout the experiment.

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Verma, S., Sharma, S., Ranawat, P. et al. Modulatory Effects of Ginkgo biloba Against Amyloid Aggregation Through Induction of Heat Shock Proteins in Aluminium Induced Neurotoxicity. Neurochem Res 45, 465–490 (2020). https://doi.org/10.1007/s11064-019-02940-z

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