Yuanhang Pan, Xinbo Zhang, Xinyu Wen, Na Yuan, Li Guo, Yifan Shi, Yuanyuan Jia, Yanzhao Guo, Fengli Hao, Shuyi Qu, Ze Chen, Lei Yang, Xiaoli Wang, Yonghong Liu
Development and validation of a machine learning model for prediction of comorbid major depression disorder among narcolepsy type 1
Sleep medicine
currently 55 million people around world suffer dementia alzheimers disease related dementias adrd accounts nearly 6070 cases spread alzheimers disease ad pathology progressive neurodegeneration hippocampus cerebral cortex strongly correlated cognitive decline ad patients however molecular underpinning adrds causality still unclear studies postmortem ad brains animal models ad suggest elevated endoplasmic reticulum er stress may role adrd pathology altered neurocellular homeostasis brain regions associated learning memory study er stressassociated neurocellular response effects neurocellular homeostasis neurogenesis modeled er stress challenge using thapsigargin tg specific inhibitor sarcoendoplasmic reticulum ca2 atpase serca induced pluripotent stem cell ipscderived neural stem cells nscs two individuals mexican american family study mafs highcontent screening transcriptomic analysis control er stresschallenged nscs showed nscs er stress response resulted significant decline nsc selfrenewal increase apoptosis cellular oxidative stress total 2300 genes significantly moderated statistics fdrcorrected pvalue 005 fold change absolute 20 differentially expressed de pathway enrichment gene network analysis de genes suggests three unfolded protein response upr pathways protein kinase rnalike er kinase perk activating transcription factor6 atf6 inositolrequiring enzyme1 ire1 significantly activated cooperatively regulated nscs transcriptional response er stress results show ire1xbox binding protein 1 xbp1 mediated transcriptional regulation e2f transcription factor 1 e2f1 gene downstream targets dominant role inducing g1sphase cell cycle arrest er stresschallenged nscs er stresschallenged nscs also showed activation cebp homologous protein chopmediated apoptosis dysregulation synaptic plasticity neurotransmitter homeostasisassociated genes overall results suggest er stressassociated attenuation nsc selfrenewal increased apoptosis dysregulated synaptic plasticity neurotransmitter homeostasis plausibly play role causation adrd