Browsing by Author "Archita Khanna"

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Epigenetic role of sirtuins in neurodegenerative brain disorders
(Elsevier, 2021) Archita Khanna; Anamika; Surendra Kumar Trigun
Sirtuins, a family of NAD+-dependent class III histone deacetylases (HDACs), are known to deacetylate some histone and nonhistone proteins including various transcription and cell signaling factors, thereby helping to regulate expression of many genes under a variety of stress challenges, and therefore they are referred to as important epigenetic regulators of the cell functions. This is in line with the classical Zn2+-dependent class I and class II HDACs, first recognized as protein level epigenetic regulators, which by modulating chromatin dynamics could affect DNA functions. All together, seven cell organelle-specific mammalian sirtuin homologues are known with distinct metabolic roles. SIRT 1, 6, and 7 are predominantly localized in the nucleus; SIRT 3, 4, and 5 are mitochondrial; while SIRT2 is found in the cytoplasm. The research during the past decade could characterize a good number of protein targets like histone H3 (H3K9), PGC1α, FOX03a, p53, and NF-κB type transcription factors for SIRT1 and SOD2, IDH2, LCAD, AceCS2, FOX03a etc. for mitochondrial SIRT3, which are now argued to be critically associated with the cell survival versus cell death mechanisms. As dysregulation of gene expression and mitochondrial dysfunction constitutes the base line of pathogenesis of many neurodegenerative brain disorders, like Alzheimer’s disease, Parkinson’s disease, Huntington’s, stroke etc., it is argued that SIRT1 and SIRT3 are likely to be the logical hot spots for exploring pathogenesis and therapeutic options against these brain disorders. Indeed some findings describe that SIRT1 and/or SIRT3 overexpression/activation could impart neuroprotection, whereas their inactivation/suppression could correlate with the neuronal derangements associated with aging and excitotoxic brain disorders. Thus sirtuin biochemistry seems to be an evolving concept in discerning the neuropathology of brain disorders. © 2021 Elsevier Inc. All rights reserved.
Mitochondrial SIRT3 and neurodegenerative brain disorders
(Elsevier B.V., 2019) Anamika; Archita Khanna; Papia Acharjee; Arup Acharjee; Surendra Kumar Trigun
Sirtuins are highly conserved NAD+ dependent class III histone deacetylases and catalyze deacetylation and ADP ribosylation of a number of non-histone proteins. Since, they require NAD+ for their activity, the cellular level of Sirtuins represents redox status of the cells and thereby serves as bona fide metabolic stress sensors. Out of seven homologues of Sirtuins identified in mammals, SIRT3, 4 & 5 have been found to be localized and active in mitochondria. During recent past, clusters of protein substrates for SIRT3 have been identified in mitochondria and thereby advocating SIRT3 as the main mitochondrial Sirtuin which could be involved in protecting stress induced mitochondrial integrity and energy metabolism. As mitochondrial dysfunction underlies the pathogenesis of almost all neurodegenerative diseases, a role of SIRT3 becomes an arguable speculation in such brain disorders. Some recent findings demonstrate that SIRT3 over expression could prevent neuronal derangements in certain in vivo and in vitro models of aging and neurodegenerative brain disorders like; Alzheimer's disease, Huntington's disease, stroke etc. Similarly, loss of SIRT3 has been found to accelerate neurodegeneration in the brain challenged with excitotoxicity. Therefore, it is argued that SIRT3 could be a relevant target to understand pathogenesis of neurodegenerative brain disorders. This review is an attempt to summarize recent findings on (1) the implication of SIRT3 in neurodegenerative brain disorders and (2) whether SIRT3 modulation could ameliorate neuropathologies in relevant models. © 2017 Elsevier B.V.
SIRT1 activation by resveratrol reverses atrophy of apical dendrites of hippocampal CA1 pyramidal neurons and neurobehavioral impairments in moderate grade hepatic encephalopathy rats
(Elsevier B.V., 2020) Archita Khanna; Anamika; Suwarna Chakraborty; Sunil Jamuna Tripathi; Arup Acharjee; Shankaranarayana Rao BS; Surendra K. Trigun
A preliminary observation about resveratrol (RSV) dependent normalization of inflammatory and apoptotic factors in the cortex of hyperammonemic rat model of moderate grade hepatic encephalopathy (MoHE) led us to evaluate whether RSV is ultimately able to confer neuroprotection against MoHE pathogenesis and that it does so by activating its bonafide molecular target SIRT1. The present study compared the profile of relevant neurobehavioral pattern vs neuromorphometry of hippocampal CA1 neurons and SIRT1 activity in the hippocampus of the chronic liver failure (CLF) model of moderate grade HE (MoHE) rats induced by administration of 100 mg/kg body weight of thioacetamide i.p. for 10 days and in the CLF/MoHE rats treated with 10 mg/kg body weight RSV i.p. for 7 days. As compared to the control group rats, the MoHE rats showed significantly deranged pattern of memory and motor functions on MWM and rota rod tests, respectively. These behavioural deficits were associated with a significant reduction in apical dendrite length and number of branching points in the CA1 pyramidal neurons. Interestingly, all these parameters were found to be recovered back to their normal levels in the MoHE rats treated with RSV. Concordantly, MoHE associated declined SIRT1 activity in the hippocampus could be normalized back due to RSV treatment to those MoHE rats. Our findings suggest that RSV is able to normalize MoHE associated memory impairments and motor deficits vis a vis reversal of CA1 dendritic atrophy via SIRT1 activation. © 2020 Elsevier B.V.