DR ANKUR SRIVASTAVA
@iitrindia.org
Research Associate in Systems Toxicology Group
CSIR-INDIAN INSTITUTE OF TOXICOLOGY RESEARCH
EDUCATION
M.Sc. in Biotechnology
Ph.D. in Biotechnology, Biochemistry, Neurobiology
RESEARCH, TEACHING, or OTHER INTERESTS
Neuroscience, General Neuroscience, Molecular Biology, Cell Biology
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Sadaf Jahan, Uzair Ahmad Ansari, Ankur Kumar Srivastava, Sahar Aldosari, Nessrin Ghazi Alabdallat, Arif Jamal Siddiqui, Andleeb Khan, Hind Muteb Albadrani, Sana Sarkar, Bushra Khan,et al.
Frontiers Media SA
Chemical-induced neurotoxicity is increasingly recognized to accelerate the development of neurodegenerative disorders (NDs), which pose an increasing health burden to society. Attempts are being made to develop drugs that can cross the blood–brain barrier and have minimal or no side effects. Nobiletin (NOB), a polymethoxylated flavonoid with anti-oxidative and anti-inflammatory effects, has been demonstrated to be a promising compound to treat a variety of NDs. Here, we investigated the potential role of NOB in sodium arsenate (NA)-induced deregulated miRNAs and target proteins in human neural progenitor cells (hNPCs). The proteomics and microRNA (miRNA) profiling was done for different groups, namely, unexposed control, NA-exposed, NA + NOB, and NOB groups. Following the correlation analysis between deregulated miRNAs and target proteins, RT-PCR analysis was used to validate the selected genes. The proteomic analysis showed that significantly deregulated proteins were associated with neurodegeneration pathways, response to oxidative stress, RNA processing, DNA repair, and apoptotic process following exposure to NA. The OpenArray analysis confirmed that NA exposure significantly altered miRNAs that regulate P53 signaling, Wnt signaling, cell death, and cell cycle pathways. The RT-PCR validation studies concur with proteomic data as marker genes associated with autophagy and apoptosis (HO-1, SQSTM1, LC-3, Cas3, Apaf1, HSP70, and SNCA1) were altered following NA exposure. It was observed that the treatment of NOB significantly restored the deregulated miRNAs and proteins to their basal levels. Hence, it may be considered one of its neuroprotective mechanisms. Together, the findings are promising to demonstrate the potential applicability of NOB as a neuroprotectant against chemical-induced neurotoxicity.
R. Negi, A. Srivastava, A. K. Srivastava, P. Vatsa, U. A. Ansari, B. Khan, H. Singh, A. Pandeya, and AB Pant
Springer Science and Business Media LLC
Ankita Srivastava, Ankur Kumar Srivastava, Abhishek Pandeya, and Aditya Bhushan Pant
Elsevier BV
R. Negi, A. Srivastava, A. Srivastava, Abhishek Pandeya, P. Vatsa, U. A. Ansari and A. Pant
BACKGROUND AND OBJECTIVES: Induced pluripotent stem cells (iPSCs) derived three-dimensional (3D) model for rare neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) is emerging as a novel alternative to human diseased tissue to explore the disease etiology and potential drug discovery. In the interest of the same, we have generated a TDP-43-mutated human iPSCs (hiPSCs) derived 3D organoid model of ALS disease. The high-resolution mass spectrometry (MS)-based proteomic approach is used to explore the differential mechanism under disease conditions and the suitability of a 3D model to study the disease. MATERIALS AND METHODS: The hiPSCs cell line was procured from a commercial source, grown, and characterized following standard protocols. The mutation in hiPSCs was accomplished using CRISPR/Cas-9 technology and predesigned gRNA. The two groups of organoids were produced by normal and mutated hiPSCs and subjected to the whole proteomic profiling by high-resolution MS in two biological replicates with three technical replicas of each. RESULTS: The proteomic analysis of normal and mutated organoids revealed the proteins associated with pathways of neurodegenerative disorders, proteasomes, autophagy, and hypoxia-inducible factor-1 signaling. Differential proteomic analysis revealed that the mutation in TDP-43 gene caused proteomic deregulation, which impaired protein quality mechanisms. Furthermore, this impairment may contribute to the generation of stress conditions that may ultimately lead to the development of ALS pathology. CONCLUSION: The developed 3D model represents the majority of candidate proteins and associated biological mechanisms altered in ALS disease. The study also offers novel protein targets that may uncloud the precise disease pathological mechanism and be considered for future diagnostic and therapeutic purposes for various neurodegenerative disorders.
Ankur Kumar Srivastava, Smriti Singh Yadav, Saumya Mishra, Sanjeev Kumar Yadav, Devendra Parmar, and Sanjay Yadav
Informa UK Limited
Abstract Zinc oxide nanoparticles (ZnO NPs) are one of the most broadly used engineered nanomaterials. The toxicity potential of ZnO NPs has been explored in several studies; however, its neurotoxicity, especially its molecular mechanism, has not been studied in depth. In this study, we have used a cellular model of neuronal differentiation (nerve growth factor differentiated PC12 cells) to compare the effect of ZnO NPs exposure on neuronal (differentiated or mature neurons) and non-neuronal (undifferentiated) cells. Our studies have shown that the noncytotoxic concentration of ZnO NPs causes neurite shortening and degeneration in differentiated PC12 cells. Brain-specific microRNA (miRNA) array and liquid chromatography with tandem mass spectrometry (LC-MS/MS) are used to carry out profiling of miRNAs and proteins in PC12 cells exposed with ZnO NPs. Exposure of ZnO NPs produced significant deregulation of a higher number of miRNAs (15) and proteins (267) in neuronal cells in comparison to miRNAs (8) and proteins (207) of non-neuronal cells (8). In silico pathway analysis of miRNAs and proteins deregulated in ZnO NPs exposed differentiated PC12 cells have shown pathways leading to neurodegenerative diseases and mitochondrial dysfunctions are primarily targeted pathways. Further, a bioenergetics study carried out using Seahorse XFp metabolic flux analyzer has confirmed the involvement of mitochondrial dysfunctions in ZnO NPs exposed differentiated PC12 cells. In conclusion, differentiated PC12 cells (neuronal) were found more vulnerable than undifferentiated (non-neuronal PC12 cells) toward the exposure of ZnO NPs and deregulation of miRNAs and mitochondrial dysfunctions play a significant role in its toxicity.
Ankita Srivastava, Ankur Kumar Srivastava, Manisha Mishra, Jai Shankar, Anita Agrahari, Mohan Kamthan, Pradhyumna K. Singh, Sanjay Yadav, and Devendra Parmar
Elsevier BV
Anurag Kumar Srivastav, Nitesh Dhiman, Hafizurrahman Khan, Ankur Kumar Srivastav, Sanjeev Kumar Yadav, Jyoti Prakash, Nidhi Arjaria, Dhirendra Singh, Sanjay Yadav, Satyakam Patnaik,et al.
Elsevier BV
Abhishek Jauhari, Tanisha Singh, Ankita Pandey, Parul Singh, Nishant Singh, Ankur Kumar Srivastava, Aditya Bhushan Pant, Devendra Parmar, and Sanjay Yadav
Springer Science and Business Media LLC
Ankita Pandey, Abhishek Jauhari, Tanisha Singh, Parul Singh, Nishant Singh, Ankur Kumar Srivastava, Farah Khan, Aditya Bhushan Pant, Devendra Parmar, and Sanjay Yadav
Oxford University Press (OUP)
Cypermethrin, a pyrethroid pesticide, has been shown to induce neurotoxicity in adult mammals. However, studies are also needed to explore its toxicity in developing brains and understand its mechanism of action in neurons.
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Industry, Institute, or Organisation Collaboration
CSIR- Indian Institute of Toxicology Research, Lucknow
National Dope Testing Laboratory, New Delhi