1. Asthma aggravates alzheimer's disease by up-regulating NF- κB signaling pathway through LTD4.
- Author
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Wang, Xiaozhen, Gan, Wenjing, Kang, Meimei, Lv, Caizhen, Zhao, Zhiwei, Wu, Yanchuan, Zhang, Xu, and Wang, Rong
- Subjects
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ALZHEIMER'S disease , *CELLULAR signal transduction , *ASTHMA , *AMYLOID beta-protein precursor , *PATHOLOGICAL physiology , *DISEASE risk factors - Abstract
[Display omitted] • Asthma aggravates the spatial learning and memory ability of APP/PS1 mice. • Asthma aggravates AD pathology and cognitive impairment of APP/PS1 mice via upregulation of NF-kB inflammatory pathway. • Montelukast relieves cognitive impairment and neuroinflammatory damage in AD aggravated by asthma. Clinical studies have shown that asthma is a risk factor for dementia or Alzheimer's disease (AD). To investigate whether asthma aggravates AD in APP/PS1 mice and explore the potential mechanisms, an asthma model was established using six-month-old APP/PS1 mice, and montelukast was used as a therapeutic agent in APP/PS1 mice with asthma. The Morris water maze test showed that asthma aggravates spatial learning and memory abilities. Asthma also upregulates the NF-κB inflammatory pathway in APP/PS1 mice and promotes the expression of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), amyloid-β (Aβ) deposition, neuronal damage, synaptic plasticity deficiency, activation of microglia and astrocytes. The level of LTD4 and its receptor CysLT1R in the hippocampus of APP/PS1 mice after the asthma modeling was established was higher than that in APP/PS1 mice, suggesting that asthma may affect the pathology of AD through LTD4 and its receptor Cys-LT1R. Montelukast ameliorates these pathological changes and cognitive impairment. These results suggest that asthma aggravates AD pathology and cognitive impairment of APP/PS1 mice via upregulation of the NF-κB inflammatory pathway, and montelukast ameliorates these pathological changes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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