title: MicroRNAs 99b-5p/100-5p Regulated by Endoplasmic Reticulum Stress are Involved in Abeta-Induced Pathologies.
abstract: Alzheimer's disease (AD) is the most common cause of dementia. Amyloid β (Abeta, Aβ) deposition and intracellular tangles are the pathological hallmarks of AD. MicroRNAs (miRNAs) are small non-coding RNAs, which have been found to play very important roles, and have the potential to serve as diagnostic markers during neuronal pathogenesis. In this study, we aimed to determine the roles of miR-99b-5p and miR-100-5p in Aβ-induced neuronal pathologies. We detected the expression levels of miR-99b-5p and miR-100-5p in the brains of APPswe/PS1ΔE9 double-transgenic mice (APP/PS1 mice) at different age stages and found that both miRNAs were decreased at early stages while increased at late stages of APP/PS1 mice when compared with the age-matched wild type (WT) mice. Similar phenomenon was also observed in Aβ-treated cultured cells. We also confirmed that mammalian target of rapamycin (mTOR) is one of the targets of miR-99b-5p/100-5p, which is consistent with previous studies in cancer. MiR-99b-5p/100-5p has been found to promote cell apoptosis with the Aβ treatment. This effect may be induced via the mTOR pathway. In our study, we find both miR-99b-5p and miR-100-5p affect neuron survival by targeting mTOR. We also speculate that dynamic change of miR-99b-5p/100-5p levels during Aβ-associated pathologies might be attributed to Aβ-induced endoplasmic reticulum stress (ER stress), suggesting the potential role of the "ER stress-miRNAs-mTOR" axis in Aβ-related AD pathogenesis.
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center , Shenzhen , China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Ye
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center , Shenzhen , China.
authors.forename: Hongxue
authors.initials: H
authors.lastname: Luo
authors.affiliation: Division of Life Science, The Hong Kong University of Science and Technology , Hong Kong , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center , Shenzhen , China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center , Shenzhen , China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center , Shenzhen , China.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Ludwig Institute for Cancer Research , San Diego, CA , USA.
authors.forename: Yarui
authors.initials: Y
authors.lastname: Diao
authors.affiliation: Division of Life Science, The Hong Kong University of Science and Technology , Hong Kong , China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Neurology, Tangdu Hospital, Fourth Military Medical University , Xi'an City , China.
authors.forename: Jianting
authors.initials: J
authors.lastname: Miao
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center , Shenzhen , China ; Division of Life Science, The Hong Kong University of Science and Technology , Hong Kong , China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wan
keywords: Alzheimer’s disease; amyloid β; endoplasmic reticulum stress; microRNA-100-5p; microRNA-99b-5p