Abstract
Accumulation of Aβ42 peptides forming plaque in various regions of the brain is a hallmark of Alzheimer’s disease (AD) progression. However, to date, there is no effective management strategy reported for attenuation of Aβ42-induced toxicity in the early stages of the disease. Alternate medicinal systems such as Ayurveda in the past few decades show promising results in the management of neuronal complications. Medhya Rasayana such as Brahmi is known for its neuroprotective properties via resolving memory-related issues, while the underlying molecular mechanism of the same remains unclear. In the present study, we aimed to understand the neuroprotective effects of the aqueous extract of Bacopa monnieri and Centella asiatica (both commonly known as Brahmi) against the Aβ42 expressing model of the Drosophila melanogaster. By applying a quantitative proteomics approach, the study identified > 90% of differentially expressed proteins from Aβ42 expressing D. melanogaster were either restored to their original expression pattern or showed no change in expression pattern upon receiving either Brahmi extract treatment. The Brahmi restored proteins were part of neuronal pathways associated with cell cycle re-entry, apoptosis, and mitochondrial dynamics. The neuroprotective effect of Brahmi was also validated by negative geotaxis behavioral analysis suggesting its protective role against behavioral deficits exerted by Aβ42 toxicity. We believe that these discoveries will provide a platform for developing novel therapeutics for AD management by deciphering molecular targets of neuroprotection conferred by an aqueous extract of Bacopa monnieri or Centella asiatica.
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Data Availability
The MS/MS raw data and the PD search data along with results files were submitted to ProteomeXchange Consortium via the PRIDE repository [70] with data set identifier PXD027101.
Abbreviations
- AD:
-
Alzheimer’s disease
- WT:
-
Wild-type/Canton S flies
- BM:
-
Bacopa monnieri Extract
- CA:
-
Centella asiatica Extract
- Aβ42:
-
Amyloid beta peptide with 42 amino acids
- WT + BM:
-
WT flies fed on Bacopa monnieri extract
- WT + CA:
-
WT flies fed on Centella asiatica extract
- Aβ42 + BM:
-
Aβ42 flies fed on Bacopa monnieri extract
- Aβ42 + CA:
-
Aβ42 flies fed on Centella asiatica extract
- TMT:
-
Tandem mass tags
- LC–MS/MS:
-
Tandem mass spectrometry
- SDS-PAGE:
-
Sodium dodecyl sulfate–polyacrylamide gel electrophoresis
- ACN:
-
Anhydrous acetonitrile
- TFA:
-
Trifluoroacetic acid
- HCD:
-
Higher-energy collision dissociation
- PD 2.2:
-
Proteome Discoverer version 2.2
- FDR:
-
False discovery rate
- PSM:
-
Peptide-spectrum matches
- FC:
-
Fold change
- GO:
-
Gene Ontology
- ETC:
-
Etectron transport chain
- PPI:
-
Protein-protein interaction network
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Acknowledgements
The authors thank Karnataka Biotechnology and Information Technology Services (KBITS), Government of Karnataka, for support to the Center for Systems Biology and Molecular Medicine at Yenepoya (Deemed to be University), Mangalore, under the Biotechnology Skill Enhancement Programme in Multiomics Technology (BiSEP GO ITD 02MDA2017). The authors also thank Yenepoya (Deemed to be University) for access to mass spectrometry instrumentation. Sayali C. Deolankar and Poornima Ramesh are the recipients of Senior Research Fellowships from the Indian Council of Medical Research (ICMR), Government of India. Mohd. Altaf Najar and Anagha Kanichery are the recipients of Senior Research Fellowships from the University Grants Commission (UGC), Government of India. Raghu SV is grateful to DBT-Ramalingaswami Re-entry Fellowship.
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All authors contributed to the study’s conception and design. TSKP and SPVR conceptualized the study, designed the experiments, and critically reviewed the manuscript. SPVR, AKK, and SCD performed fly treatment, experiment, and protein extraction from fly heads. SCD, MAN, PR, and AK carried out proteomics sample preparation, fractionation, and mass spectrometry. SCD and MAN analyzed mass spectrometry-based data. SCD prepared figures and tables, and wrote the manuscript. All the authors read and revised the manuscript for important intellectual content and approved the final manuscript.
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This study was approved by Yenepoya Ethics Committee-1, Yenepoya (Deemed to be University), with Ethical clearance protocol no. YEC-1/2021/006.
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Deolankar, S.C., Najar, M.A., Ramesh, P. et al. Discovery of Molecular Networks of Neuroprotection Conferred by Brahmi Extract in Aβ42-Induced Toxicity Model of Drosophila melanogaster Using a Quantitative Proteomic Approach. Mol Neurobiol 60, 303–316 (2023). https://doi.org/10.1007/s12035-022-03066-0
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DOI: https://doi.org/10.1007/s12035-022-03066-0