Browsing by Author "Sandeep Kumar Dubey"

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A Case of Vertigo with TORP in Inner Ear
(Springer, 2023) Ramraj Yadav; Rajesh Kumar; Sunil Kumar; Deepak Kumar Gupta; Vishwambhar Singh; Ashvanee Kumar Chaudhary; Sandeep Kumar Dubey; Satya Prakash Verma; A. Aruna
This is a case of a patient with history of ear surgery who visited ENT outdoor, for continuous vertigo which used to get aggravated with loud noise, associated with hearing loss, persistent sensations of right-sided aural fullness/pressure and otalgia for last 2 years. He had history of tympanoplasty with ossiculoplasty using a TORP. On exploration under local anesthesia there was a displaced prosthesis into inner ear, upon removal of which symptoms and severity subsided exponentially. © 2023, Association of Otolaryngologists of India.
Disrupted nuclear import of cell cycle proteins in Huntington's/PolyQ disease causes neurodevelopment defects in cellular and Drosophila model
(Elsevier Ltd, 2024) Sandeep Kumar Dubey; Thomas E. Lloyd; Madhu G. Tapadia
Huntington's disease is caused by an expansion of CAG repeats in exon 1 of the huntingtin gene encoding an extended PolyQ tract within the Huntingtin protein (mHtt). This expansion results in selective degeneration of striatal medium spiny projection neurons in the basal ganglia. The mutation causes abnormalities during neurodevelopment in human and mouse models. Here, we report that mHtt/PolyQ aggregates inhibit the cell cycle in the Drosophila brain during development. PolyQ aggregates disrupt the nuclear pore complexes of the cells preventing the translocation of cell cycle proteins such as Cyclin E, E2F and PCNA from cytoplasm to the nucleus, thus affecting cell cycle progression. PolyQ aggregates also disrupt the nuclear pore complex and nuclear import in mHtt expressing mammalian CAD neurons. PolyQ toxicity and cell cycle defects can be restored by enhancing RanGAP-mediated nuclear import, suggesting a potential therapeutic approach for this disease. © 2024
Yorkie Regulates Neurodegeneration Through Canonical Pathway and Innate Immune Response
(Humana Press Inc., 2018) Sandeep Kumar Dubey; Madhu G. Tapadia
Expansion of CAG repeats in certain genes has long been known to be associated with neurodegenerastion, but the quest to identity the underlying mechanisms is still on. Here, we analyzed the role of Yorkie, the coactivator of the Hippo pathway, and provide evidence to state that it is a robust genetic modifier of polyglutamine (PolyQ)-mediated neurodegeneration. Yorkie reduces the pathogenicity of inclusion bodies in the cell by activating cyclin E and bantam, rather than by preventing apoptosis through DIAP1. PolyQ aggregates inhibit Yorkie functioning at the protein, rather than the transcript level, and this is probably accomplished by the interaction between PolyQ and Yorkie. We show that PolyQ aggregates upregulate expression of antimicrobial peptides (AMPs) and Yorkie negatively regulates immune deficiency (IMD) and Toll pathways through relish and cactus, respectively, thus reducing AMPs and mitigating PolyQ affects. These studies strongly suggest a novel mechanism of suppression of PolyQ-mediated neurotoxicity by Yorkie through multiple channels. © 2017, Springer Science+Business Media New York.