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ABSTRACT
Objectives: Long-non-coding RNAs (lncRNAs) have been involved in central nervous system recently. A number of studies have reported that lncRNA NEAT1 exerts critical roles in neurodegenerative disorder. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) has been reported to exert function in the accumulation of amyloid-β (Aβ). Moreover, BACE1 acts as a target of miR-124 in the progression of AD. So far, the biological role and underlying mechanisms of NEAT1 and miR-124 in AD remains elusive.
Methods: The relative NEAT1 and miR-124 expression was examined by qRT-PCR in the tissues and cells line of AD. Cell apoptosis was examined by FACS. Luciferase reporter assay was performed to verify that miR-124 is a direct target of NEAT1, and BACE1 is a downstream target of miR-124. qRT-PCR and western blot analysis were also performed to determinate the BACE1 and the phosphorylation of tau protein.
Results: NEAT1 was notably up-regulated and miR-124 was remarkably down-regulated in AD mouse model. Knockdown of NEAT1 or overexpression of miR-124 showed the protective effects on cellular AD model induced by Aβ. Moreover, miR-124 expression could be up- and down-regulated by suppression or overexpression of NEAT1, respectively. In addition, the expression of BACE1 was the potential functional target of miR-124. These findings suggested that NEAT1 might play a vital role in the development of AD by regulating miR-124/BACE1 axis.
Discussion: The present study showed that NEAT1 worked as a regulating factor to promote the development of AD via modulating miR-124/BACE1 axis, which might be considered as a novel target in AD treatment.
Acknowledgment
We would like to give our sincere gratitude to the reviewers for their constructive comments.
Disclosure statement
No potential conflict of interest was reported by the authors.
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Notes on contributors
Mei-Ying Zhao
Mei-Ying Zhao, earned her bachelor degree in clinical medicine at Xinxiang medical college in 2001, and went to earn her M.D in neurology from Sichuan University, researching Stroke. She is dedicated to excellence in clinical neurophysiology. Her practice includes general neurology with a special interest in neuromuscular disease. Her research interests include Alzheimer’s disease, ALS, myasthenia gravis, neuropathy, and stroke. She has several publications in therapy of Alzheimer’s disease and stroke. She has also presented numerous posters at national and international neurological conferences regarding ALS, Alzheimer’s disease. She also provides continuing education lecture regarding Alzheimer’s assessment to clinical medical students at Zhengzhou university.
Gui-Qing Wang
Gui-Qing Wang, Gui-Qing Wang earned her bachelor degree in clinical medicine at Zhengzhou University in 1997. She is dedicated to excellence inclinical neurophysiology. Her practice includes general neurology with a special interest in neuromuscular disease. Her research interests include Alzheimer’s disease, Parkinson’s disease, myasthenia gravis, neuropathy, and stroke. She has several publications in therapy of Alzheimer’s disease and stroke. She has also presented numerous posters at national and international neurological conferences regarding Parkinson’s diseased and Alzheimer’s disease. She also provides continuing education lecture regarding Alzheimer’s assessment to clinical medical students at Zhengzhou University.
Ni-Ni Wang
Ni-Ni Wang, earned her bachelor degree in clinical medicine at Xinxiang medical college in 2004, and went to earn her M.D in neurology from Central South University, researching Stroke. She is dedicated to excellence in clinical neurophysiology. Her practice includes general neurology with a special interest in cerebrovascular disease. Her research interests include Alzheimer’s disease and stroke. She has one publication in therapy of stroke.
Qiao-Yan Yu
Qiao-Yan Yu, earned her bachelor degree in the-seven-year clinical medicine at China Medical University in 2012, researching cerebrovascular disease. She is dedicated to excellence in clinical neurophysiology. She is working on demyelinating diseases. Her research includes optic neuromyelitis, multiple sclerosis, pseudomyelinosis, autoimmune encephalitis and more. She has published several articles in important national journals. She is also responsible for reading the electroencephalogram in the department.
Rong-Li Liu
Rong-Li Liu, earned her bachelor degree in clinical medicine at Zhengzhou University in 2009, and went to earn her M.D in neurology from The First Affiliated Hospital of Zhengzhou University, researching Stroke. Her practice includes general neurology with a special interest in neuromuscular disease. Her research interests include Alzheimer’s disease, ALS, and stroke. She has several publications in therapy of stroke. She has also presented numerous posters at national and international neurological conferences regarding ALS, Alzheimer’s disease.
Wen-Qian Shi
Wen-Qian Shi, earned her bachelor degree in clinical medicine at Nantong medical college in 2010, and went to earn her M.D in neurology from Anhui medical university, researching Stroke. She is dedicated to excellence in clinical neurophysiology. Her practice includes general neurology with a special interest in parkinson’s disease. Her research interests include Alzheimer’s disease, multiple sclerosis, epilepsy, and stroke. She has several publications in therapy of Alzheimer’s disease and stroke. She has also presented numerous posters at national neurological conferences regarding Alzheimer’s disease.