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29 results on '"Dheer, Yogita"'

2. Upregulation of Proteolytic Pathways and Altered Protein Biosynthesis Underlie Retinal Pathology in a Mouse Model of Alzheimer’s Disease

Author

Mirzaei, Mehdi, Pushpitha, Kanishka, Deng, Liting, Chitranshi, Nitin, Gupta, Veer, Rajput, Rashi, Mangani, Abu Bakr, Dheer, Yogita, Godinez, Angela, McKay, Matthew J., Kamath, Karthik, Pascovici, Dana, Wu, Jemma X., Salekdeh, Ghasem Hosseini, Karl, Tim, Haynes, Paul A., Graham, Stuart L., and Gupta, Vivek K.

Published
2019
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6. Understanding the retinoid-x-receptor biology and manipulating it as a novel strategy to protect the retina

Author

Dheer, Yogita

Subjects
genetic structures, sense organs, Other education not elsewhere classified, eye diseases
Abstract

Glaucoma is a degenerative optic neuropathy affecting nearly 80 million individuals by 2020 worldwide. Glaucoma is mainly manifested as alterations of the optic disc with progressive degeneration of retinal ganglion cells (RGCs) contributing to visual field loss. High intraocular pressure (IOP) is considered as the main risk factor of glaucoma. Unfortunately, a significant number of patients show disease progression despite treating with IOP lowering drugs. So, RGC degeneration cannot be prevented only by reducing eye pressure. There is need for development of more novel strategies targeting retinal neuroprotection. Within this context, this PhD project aimed to assess the potential neuroprotective effect of RXR activation by its agonist bexarotene both in vitro studies as well as in vivo acute and chronic glaucoma models. Retinoid X receptors (RXRs) are ligand-dependent transcription factors that belong to the nuclear receptor (NR) superfamily. RXRs have three different isoforms (α, β, and γ) and can form both homo- and heterodimers with other nuclear receptors. Numerous studies have linked RXR modulation with neuroprotection. This thesis was mainly focused to elucidate the role of bexarotene as RXR modulator in glaucoma pathology. In first part of this study I demonstrated the expression and regulation of RXR receptors in SH-SY5Y cells using different concentrations of bexarotene. I also studied the role of TrkB signalling with RXR pathway in regulating endoplasmic reticulum stress response and apoptotic pathway activation. The results obtained from in vitro studies demonstrated that optimum concentrations of bexarotene upregulated the expression of all the three isoforms of RXRs. Also my studies revealed that higher concentrations of bexarotene upregulates ER stress proteins and BAD which can be prevented by pharmacological targeting of the TrkB receptor. I further extended my studies to assess the neuroprotective effects of RXR activation in mice in preventing loss of retinal ganglion cells (RGCs) under experimental glaucoma conditions. Two models i.e increased excitotoxicity mediated glutamate model (acute model) and microbead induced increased intraocular pressure model (chronic 2 months model) of RGC degeneration were used for in vivo studies. Bexarotene treatment showed enhanced expression of RXRs as compared to control and glaucoma mice retinal sections. Furthermore it was seen that bexarotene maintained inner retinal functional and structural integrity confirmed by electroretinography, H and E staining and Bieschowlsky silver staining of optic nerve sections. Moreover, docking studies also validated binding of bexarotene to RXR receptors. This thesis represents an integration of three different methodologies i.e in vitro, in vivo, in silico. The results from this thesis provide evidence to the hypothesis that RXR activation can be neuroprotective to RGCs in preventing apoptosis and cell death. Bexarotene or other RXR agonists may have potential for future therapeutic management of glaucoma.

Published
2022
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7. Cell cycle deficits in neurodegenerative disorders: uncovering molecular mechanisms to drive innovative therapeutic development

Author

Joseph, Chitra, Mangani, Abubakar Siddiq, Gupta, Veer, Chitranshi, Nitin, Shen, Ting, Dheer, Yogita, Devaraj, KB, Mirzaei, Mehdi, You, Yuyi, Graham, Stuart L, Gupta, Vivek, Joseph, Chitra, Mangani, Abubakar Siddiq, Gupta, Veer, Chitranshi, Nitin, Shen, Ting, Dheer, Yogita, Devaraj, KB, Mirzaei, Mehdi, You, Yuyi, Graham, Stuart L, and Gupta, Vivek

Published
2020

11. Amyloid β Induces Early Changes in the Ribosomal Machinery, Cytoskeletal Organization and Oxidative Phosphorylation in Retinal Photoreceptor Cells

Author

Deng, Liting, primary, Pushpitha, Kanishka, additional, Joseph, Chitra, additional, Gupta, Veer, additional, Rajput, Rashi, additional, Chitranshi, Nitin, additional, Dheer, Yogita, additional, Amirkhani, Ardeshir, additional, Kamath, Karthik, additional, Pascovici, Dana, additional, Wu, Jemma X., additional, Salekdeh, Ghasem Hosseini, additional, Haynes, Paul A., additional, Graham, Stuart L., additional, Gupta, Vivek K., additional, and Mirzaei, Mehdi, additional

Published
2019
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14. Demyelination precedes axonal loss in the transneuronal spread of human neurodegenerative disease

Author

You, Yuyi, primary, Joseph, Chitra, additional, Wang, Chenyu, additional, Gupta, Vivek, additional, Liu, Sidong, additional, Yiannikas, Con, additional, Chua, Brian E, additional, Chitranshi, Nitin, additional, Shen, Ting, additional, Dheer, Yogita, additional, Invernizzi, Alessandro, additional, Borotkanics, Robert, additional, Barnett, Michael, additional, Graham, Stuart L, additional, and Klistorner, Alexander, additional

Published
2019
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17. Glaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin

Author

Gupta, Vivek, Mirzaei, Mehdi, Gupta, Veer B., Chitranshi, Nitin, Dheer, Yogita, Vander Wall, Roshana, Abbasi, Mojdeh, You, Yuyi, Chung, Roger, Graham, Stuart L., Gupta, Vivek, Mirzaei, Mehdi, Gupta, Veer B., Chitranshi, Nitin, Dheer, Yogita, Vander Wall, Roshana, Abbasi, Mojdeh, You, Yuyi, Chung, Roger, and Graham, Stuart L.

Abstract

Neuroserpin is a serine protease inhibitor that regulates the activity of plasmin and its activators in the neuronal tissues. This study provides novel evidence of regulatory effect of the neuroserpin on plasmin proteolytic activity in the retina in glaucoma. Human retinal and vitreous tissues from control and glaucoma subjects as well as retinas from experimental glaucoma rats were analysed to establish changes in plasmin and neuroserpin activity. Neuroserpin undergoes oxidative inactivation in glaucoma which leads to augmentation of plasmin activity. Neuroserpin contains several methionine residues in addition to a conserved reactive site methionine and our study revealed enhanced oxidation of Met residues in the serpin under glaucoma conditions. Met oxidation was associated with loss of neuroserpin inhibitory activity and similar findings were observed in the retinas of superoxide dismutase (SOD) mutant mice that have increased oxidative stress. Treatment of purified neuroserpin with H2O2 further established that Met oxidation inversely correlated with its plasmin inhibitory activity. Dysregulation of the plasmin proteolytic system associated with increased degradation of the extracellular matrix (ECM) proteins in the retina. Collectively, these findings delineate a novel molecular basis of plasmin activation in glaucoma and potentially for other neuronal disorders with implications in disease associated ECM remodelling.

Published
2017

19. Age-related neurodegenerative disease associated pathways identified in retinal and vitreous proteome from human glaucoma eyes

Author

Mirzaei, Mehdi, primary, Gupta, Veer B., additional, Chick, Joel M., additional, Greco, Todd M., additional, Wu, Yunqi, additional, Chitranshi, Nitin, additional, Wall, Roshana Vander, additional, Hone, Eugene, additional, Deng, Liting, additional, Dheer, Yogita, additional, Abbasi, Mojdeh, additional, Rezaeian, Mahdie, additional, Braidy, Nady, additional, You, Yuyi, additional, Salekdeh, Ghasem Hosseini, additional, Haynes, Paul A., additional, Molloy, Mark P., additional, Martins, Ralph, additional, Cristea, Ileana M., additional, Gygi, Steven P., additional, Graham, Stuart L., additional, and Gupta, Vivek K., additional

Published
2017
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22. Loss of Shp2 Rescues BDNF/TrkB Signaling and Contributes to Improved Retinal Ganglion Cell Neuroprotection

Author

Chitranshi, Nitin, Dheer, Yogita, Mirzaei, Mehdi, Wu, Yunqi, Salekdeh, Ghasem H., Abbasi, Mojdeh, Gupta, Veer, Vander Wall, Roshana, You, Yuyi, Graham, Stuart L., and Gupta, Vivek

Abstract

Glaucoma is characterized by the loss of retinal ganglion cells (RGC), and accordingly the preservation of RGCs and their axons has recently attracted significant attention to improve therapeutic outcomes in the disease. Here, we report that Src homology region 2-containing protein tyrosine phosphatase 2 (Shp2) undergoes activation in the RGCs, in animal model of glaucoma as well as in the human glaucoma tissues and that Shp2 dephosphorylates tropomyosin receptor kinase B (TrkB) receptor, leading to reduced BDNF/TrkB neuroprotective survival signaling. This was elucidated by specifically modulating Shp2 expression in the RGCs in vivo, using adeno-associated virus serotype 2 (AAV2) constructs. Shp2 upregulation promoted endoplasmic reticulum (ER) stress and apoptosis, along with functional and structural deficits in the inner retina. In contrast, loss of Shp2 decelerated the loss of RGCs, preserved their function, and suppressed ER stress and apoptosis in glaucoma. This report constitutes the first identification of Shp2-mediated TrkB regulatory mechanisms in the RGCs that can become a potential therapeutic target in both glaucoma and other neurodegenerative disorders.

Published
2024
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23. Molecular determinants and interaction data of cyclic peptide inhibitor with the extracellular domain of TrkB receptor

Author

Chitranshi, Nitin, Gupta, Vivek, Dheer, Yogita, Gupta, Veer, Vander Wall, Roshana, Graham, Stuart, Chitranshi, Nitin, Gupta, Vivek, Dheer, Yogita, Gupta, Veer, Vander Wall, Roshana, and Graham, Stuart

Abstract

TrkB is a high affinity receptor for the brain derived neurotrophic factor (BDNF) and its phosphorylation stimulates activation of several intracellular signalling pathways linked to cellular growth, differentiation and maintenance. Identification of various activators and inhibitors of the TrkB receptor and greater understanding their binding mechanisms is critical to elucidate the biochemical and pharmacological pathways and analyse various protein crystallization studies. The data presented here is related to the research article entitled "Brain Derived neurotrophic factor is involved in the regulation of glycogen synthase kinase 3β (GSK3β) signalling" [1]. Cyclotraxin B (CTXB) is a disulphide bridge linked cyclic peptide molecule that interacts with TrkB receptor and inhibits the BDNF/TrkB downstream signalling. This article reports for the first time binding mechanism and interaction parameters of CTXB with the TrkB receptor. The molecular model of CTXB has been generated and it's docking with TrkB domain carried out to determine the critical residues involved in the protein peptide interaction. © 2016 The Authors.

Published
2016

26. Glaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin

Author

Gupta, Vivek, Mirzaei, Mehdi, Gupta, Veer B., Chitranshi, Nitin, Dheer, Yogita, Vander Wall, Roshana, Abbasi, Mojdeh, You, Yuyi, Chung, Roger, Graham, Stuart L., Gupta, Vivek, Mirzaei, Mehdi, Gupta, Veer B., Chitranshi, Nitin, Dheer, Yogita, Vander Wall, Roshana, Abbasi, Mojdeh, You, Yuyi, Chung, Roger, and Graham, Stuart L.

Abstract

Gupta, V., Mirzaei, M., Gupta, V. B., Chitranshi, N., Dheer, Y., Vander Wall, R., ... & Graham, S. (2017). Glaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin. Scientific Reports, 7. (Article number 8412). Available here.

27. Computational analysis unravels novel destructive single nucleotide polymorphisms in the non-synonymous region of human caveolin gene

Author

Chitranshi, Nitin, Dheer, Yogita, Wall, Roshana V., Gupta, Veer B., Abbasi, Mojdeh, Graham, Stuart L., Gupta, Vivek K., Chitranshi, Nitin, Dheer, Yogita, Wall, Roshana V., Gupta, Veer B., Abbasi, Mojdeh, Graham, Stuart L., and Gupta, Vivek K.

Abstract

Chitranshi, N., Dheer, Y., Vander Wall, R., Gupta, V., Abbasi, M., Graham, S. L., & Gupta, V. (2016). Computational analysis unravels novel destructive single nucleotide polymorphisms in the non-synonymous region of human caveolin gene. Gene Reports. 6, 142-157. Available here.

28. Bexarotene modulates retinoid-x-receptor expression and is protective against neurotoxic endoplasmic reticulum stress response and apoptotic pathway activation

Author

Dheer, Yogita, Chitranshi, Nitin, Gupta, Veer, Abbasi, Mojdeh, Mirzaei, Mehdi, You, Yuyi, Chung, Roger, Graham, Stuart L, Gupta, Vivek, Dheer, Yogita, Chitranshi, Nitin, Gupta, Veer, Abbasi, Mojdeh, Mirzaei, Mehdi, You, Yuyi, Chung, Roger, Graham, Stuart L, and Gupta, Vivek

Abstract

Dheer, Y., Chitranshi, N., Gupta, V., Abbasi, M., Mirzaei, M., You, Y., ... & Gupta, V. (2018). Bexarotene modulates retinoid-x-receptor expression and is protective against neurotoxic endoplasmic reticulum stress response and apoptotic pathway activation. Molecular neurobiology, 55(12). 9043-9056. Available here

29. PTPN11 induces endoplasmic stress and apoptosis in SH-SY5Y cells

Author

Chitranshi, Nitin, Dheer, Yogita, Gupta, Veer, Abbasi, Mojdeh, Mirzaei, Mehdi, You, Yuyi, Chung, Roger, Graham, Stuart L., Gupta, Vivek, Chitranshi, Nitin, Dheer, Yogita, Gupta, Veer, Abbasi, Mojdeh, Mirzaei, Mehdi, You, Yuyi, Chung, Roger, Graham, Stuart L., and Gupta, Vivek

Abstract

Chitranshi, N., Dheer, Y., Gupta, V., Abbasi, M., Mirzaei, M., You, Y., ... & Gupta, V. (2017). PTPN11 induces endoplasmic stress and apoptosis in SH-SY5Y cells. Neuroscience, 364, 175-189. Available here.

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