Sirtuins functions in central nervous system cells under neurological disorders

Yan, Jing; Tang, Xiaole; Zhou, Zhiqiang; Zhang, Jie; Zhao, Yilin; Li, Shiyong; Luo, Ailin

doi:10.3389/fphys.2022.886087

Cited by 5 publications

(2 citation statements)

References 126 publications

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“…Firstly, chemotherapy can induce the production of reactive oxygen species (ROS) and oxidative stress, which can damage cellular components, including neurons. SIRT1 acts as a defender by activating cellular defense mechanisms, including the expression of antioxidant enzymes [12]. Secondly, inflammatory responses triggered by chemotherapy contribute to cognitive impairment.…”

Section: Resultsmentioning

confidence: 99%

Mangiferin-Mediated Sirtuin Modulation in Chemotherapy-Induced Cognitive Impairment: Insights from Computational Analysis

Reddy

Mutalik

et al. 2023

Preprint

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Context: Chemobrain, known as chemotherapy-induced cognitive impairment (CICI), is among the adverse effects of chemotherapy frequently observed in chronic breast cancer survivors. This condition is primarily attributed to the increased presence of free oxygen radicals and inflammatory cytokines both peripherally and centrally. SIRT1, a highly conserved evolutionary regulator, plays a pivotal role in protecting organisms from oxidative stress. Notably, elevated levels of SIRT1 are expressed in the hippocampal regions of the brain, a critical structure closely associated with learning and memory in the central nervous system. This correlation suggests that SIRT1 is implicated in the regulation of various cognitive disability models. Therefore, modulating SIRT1 activity has the potential to mitigate CICI by reducing oxidative stress markers within the brain. Method: The current study involves molecular docking of Mangiferin and other phytochemicals previously established as activators of human SIRT1 protein. Subsequently, molecular dynamics simulations are conducted using the phytochemical that exhibited the highest docking score compared to others. These investigations encompass several key steps, including protein selection, protein and ligand preparation, receptor grid generation, ligand docking, calculation of binding free energy, and molecular dynamic simulation by using using Maestro version 12.1 using Schrodinger, LLC.

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Section: Resultsmentioning

confidence: 99%

Mangiferin-Mediated Sirtuin Modulation in Chemotherapy-Induced Cognitive Impairment: Insights from Computational Analysis

Reddy

Mutalik

et al. 2023

Preprint

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“…Fibroblast growth factors (FGFs) are key signaling molecules in brain development that, in the adult stage, primarily have a homeostatic role in tissue repair and cellular proliferation [ 80 ]. Like FGFs, sirtuins are important signaling-modulating proteins with important roles in functions like cellular response to stress, CNS homeostasis, and normal brain function [ 81 , 82 ]. Wnt/β-catenin signaling is critical to neuronal survival and neurogenesis and functions in regulating synaptic plasticity, and its suppression is correlated with Alzheimer’s disease [ 83 , 84 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomics Analysis of Proteotoxic Stress Response in In-Vitro Human Neuronal Models

Alaiya,

Alharbi,

Shinwari

et al. 2024

IJMS

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Heat stroke, a hazardous hyperthermia-related illness, is characterized by CNS injury, particularly long-lasting brain damage. A root cause for hyperthermic neurological damage is heat-induced proteotoxic stress through protein aggregation, a known causative agent of neurological disorders. Stress magnitude and enduring persistence are highly correlated with hyperthermia-associated neurological damage. We used an untargeted proteomic approach using liquid chromatography–tandem mass spectrometry (LC-MS/MS) to identify and characterize time-series proteome-wide changes in dose-responsive proteotoxic stress models in medulloblastoma [Daoy], neuroblastoma [SH-SY5Y], and differentiated SH-SY5Y neuron-like cells [SH(D)]. An integrated analysis of condition–time datasets identified global proteome-wide differentially expressed proteins (DEPs) as part of the heat-induced proteotoxic stress response. The condition-specific analysis detected higher DEPs and upregulated proteins in extreme heat stress with a relatively conservative and tight regulation in differentiated SH-SY5Y neuron-like cells. Functional network analysis using ingenuity pathway analysis (IPA) identified common intercellular pathways associated with the biological processes of protein, RNA, and amino acid metabolism and cellular response to stress and membrane trafficking. The condition-wise temporal pathway analysis in the differentiated neuron-like cells detects a significant pathway, functional, and disease association of DEPs with processes like protein folding and protein synthesis, Nervous System Development and Function, and Neurological Disease. An elaborate dose-dependent stress-specific and neuroprotective cellular signaling cascade is also significantly activated. Thus, our study provides a comprehensive map of the heat-induced proteotoxic stress response associating proteome-wide changes with altered biological processes. This helps to expand our understanding of the molecular basis of the heat-induced proteotoxic stress response with potential translational connotations.

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Caffeine upregulates SIRT3 expression to ameliorate astrocytes-mediated HIV-1 Tat neurotoxicity via suppression of EGR1 signaling pathway

Gao,

Sun,

Zhang

et al. 2024

J. Neurovirol.

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Sirtuins functions in central nervous system cells under neurological disorders

Cited by 5 publications

References 126 publications

Mangiferin-Mediated Sirtuin Modulation in Chemotherapy-Induced Cognitive Impairment: Insights from Computational Analysis

Mangiferin-Mediated Sirtuin Modulation in Chemotherapy-Induced Cognitive Impairment: Insights from Computational Analysis

Proteomics Analysis of Proteotoxic Stress Response in In-Vitro Human Neuronal Models

Caffeine upregulates SIRT3 expression to ameliorate astrocytes-mediated HIV-1 Tat neurotoxicity via suppression of EGR1 signaling pathway

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