Background: Cellular damage gradually accumulates with aging, promoting a time-dependent functional decline of the brain. Microglia play an essential regulatory role in maintaining cognitive activity by phagocytosing cell debris and apoptotic cells during neurogenesis. The activities of different histone deacetylases (HDACs) regulate microglial function during development and neurodegeneration. However, no studies have described the role of HDACs in microglia during physiological aging.
Research Design And Methods: HDAC and microglial marker levels were examined in microglial cells after inducing senescence and in mouse and human hippocampal biopsies , using quantitative real-time PCR. Publicly available datasets were used to determine HDAC expression in different brain areas during physiological aging.
Results: HDAC expression increased upon the induction of senescence with bleomycin or serial passage in microglial cultures. High levels of HDACs were detected in mice and aged human brain samples. Human hippocampal samples showed a positive correlation between the expression of , and and microglial and senescence markers. and levels are enriched in the purified aged microglial population.
Conclusions: Several HDACs, particularly HDAC1, are elevated in microglia upon senescence induction and with aging , and correlate with microglial and senescence biomarkers.
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http://dx.doi.org/10.1080/14728222.2022.2158081 | DOI Listing |
Bioorg Chem
December 2024
The State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, 518132, China; School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.
The down-regulation of p21 after long-term CDK4/6 inhibition represents a key mechanism causing resistance to CDK4/6 inhibitors in some tumor cells, while the HDAC inhibitor could upregulate the level of p21. Herein, a series of novel CDK4/6 and HDAC dual-targeting inhibitors based on the moiety of palbociclib were designed and synthesized. Among them, compound N14 potently inhibited CDK4/6 and HDAC1/6 at nanomolar levels and induced cell apoptosis and G/G phase arrest through HDAC-p21-CDK signaling pathway in HuH-7 cell line.
View Article and Find Full Text PDFPlant Physiol Biochem
December 2024
Key Laboratory of Horticultural Crop Biology and Genetic Improvement (East China) of MOAR, College of Horticulture, Sanya Institute, Nanjing Agricultural University, Nanjing 210095, PR China. Electronic address:
Radish is an economically important root vegetable crop worldwide. Histone deacetylases (HDACs), one of the most important epigenetic regulators, play prominent roles in plant growth and development as well as abiotic stress responses. Nevertheless, the systematical characterization and critical roles of HDAC gene members in thermogenesis remains elusive in radish.
View Article and Find Full Text PDFDiscov Oncol
December 2024
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Background: Low-grade glioma (LGG) is a slow-growing but invasive tumor that affects brain function. Histone deacetylases (HDACs) play a critical role in gene regulation and tumor progression. This study aims to develop a prognostic model based on HDAC-related genes to aid in risk stratification and predict therapeutic responses.
View Article and Find Full Text PDFBiomol Ther (Seoul)
January 2025
Department of Biochemistry, College of Medicine, and Jeju Natural Medicine Research Center, Jeju National University, Jeju 63243, Republic of Korea.
γ-Radiation resistance is a major obstacle to the success of radiotherapy in colorectal cancer. Antioxidant-related factors contribute to resistance to radiation therapy and, therefore, are targets for improving the therapeutic response. In this study, we evaluated the molecular mechanisms underlying γ-radiation resistance using the colorectal cancer cell line SNUC5 and γ-radiation-resistant variant SNUC5/RR, including analyses of the role of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that regulates antioxidant enzymes, and related epigenetic regulators.
View Article and Find Full Text PDFEur J Med Chem
December 2024
Department of Orthopaedics, Taizhou School of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Nanjing Medical University, 366 Taihu Road, Taizhou, Jiangsu, China. Electronic address:
Histone deacetylase (HDAC) inhibitors are a promising class of epigenetic modulators in cancer therapy. This review provides a comprehensive analysis of recent synthetic strategies and clinical applications of key HDAC inhibitors for oncology. HDACs play a critical role in modulating chromatin structure and gene expression by removing acetyl groups from histone proteins, leading to transcriptional repression of tumor suppressor genes.
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