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The role of cellular senescence in neurodegenerative diseases.
Wang, Yating; Kuca, Kamil; You, Li; Nepovimova, Eugenie; Heger, Zbynek; Valko, Marian; Adam, Vojtech; Wu, Qinghua; Jomova, Klaudia.
Affiliation
  • Wang Y; College of Life Science, Yangtze University, Jingzhou, 434025, China.
  • Kuca K; Department of Chemistry, Faculty of Science, University of Hradec Králové, 500 03, Hradec Králové, Czech Republic.
  • You L; Biomedical Research Center, University Hospital Hradec Kralove, 500 05, Hradec Kralove, Czech Republic.
  • Nepovimova E; Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI), University of Granada, Granada, Spain.
  • Heger Z; College of Physical Education and Health, Chongqing College of International Business and Economics, Chongqing, 401520, China.
  • Valko M; Department of Chemistry, Faculty of Science, University of Hradec Králové, 500 03, Hradec Králové, Czech Republic.
  • Adam V; Department of Chemistry and Biochemistry, Mendel University in Brno, 613 00, Brno, Czech Republic.
  • Wu Q; Faculty of Chemical and Food Technology, Slovak University of Technology, 812 37, Bratislava, Slovakia.
  • Jomova K; Department of Chemistry and Biochemistry, Mendel University in Brno, 613 00, Brno, Czech Republic.
Arch Toxicol ; 98(8): 2393-2408, 2024 Aug.
Article in En | MEDLINE | ID: mdl-38744709
ABSTRACT
Increasing evidence has revealed that cellular senescence drives NDs, including Alzheimer's disease (AD) and Parkinson's disease. Different senescent cell populations secrete senescence-associated secretory phenotypes (SASP), including matrix metalloproteinase-3, interleukin (IL)-1α, IL-6, and IL-8, which can harm adjacent microglia. Moreover, these cells possess high expression levels of senescence hallmarks (p16 and p21) and elevated senescence-associated ß-galactosidase activity in in vitro and in vivo ND models. These senescence phenotypes contribute to the deposition of ß-amyloid and tau-protein tangles. Selective clearance of senescent cells and SASP regulation by inhibiting p38/mitogen-activated protein kinase and nuclear factor kappa B signaling attenuate ß-amyloid load and prevent tau-protein tangle deposition, thereby improving cognitive performance in AD mouse models. In addition, telomere shortening, a cellular senescence biomarker, is associated with increased ND risks. Telomere dysfunction causes cellular senescence, stimulating IL-6, tumor necrosis factor-α, and IL-1ß secretions. The forced expression of telomerase activators prevents cellular senescence, yielding considerable neuroprotective effects. This review elucidates the mechanism of cellular senescence in ND pathogenesis, suggesting strategies to eliminate or restore senescent cells to a normal phenotype for treating such diseases.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cellular Senescence / Neurodegenerative Diseases Limits: Animals / Humans Language: En Journal: Arch Toxicol Year: 2024 Document type: Article Affiliation country: China Country of publication: Germany

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cellular Senescence / Neurodegenerative Diseases Limits: Animals / Humans Language: En Journal: Arch Toxicol Year: 2024 Document type: Article Affiliation country: China Country of publication: Germany