title: miR-124 Regulates the Expression of BACE1 in the Hippocampus Under Chronic Cerebral Hypoperfusion.
abstract: Chronic cerebral hypoperfusion (CCH) is a high-risk factor of Alzheimer's disease (AD). MicroRNAs (miRNAs) are ideal mediators of hypoxic stress responses to facilitate cellular adaptation to long-term hypoxia. MiR-124 is a kind of nervous system-specific miRNAs, and one of its target genes is β-site amyloid precursor protein cleaving enzyme 1 (BACE1). In the present study, miR-124 was found to be inhibited all the time from early to late stage of cerebral hypoxia accompanying with the upregulation of BACE1 protein and overproduction of amyloid-β (Aβ) in the hippocampus from cerebral hypoperfusion rat models. Meanwhile, Aβ could further enhance the expression of BACE1 protein due to the inhibition of miR-124. Thus, miR-124 was the key factor in this hypoxia/Aβ-miR-124-BACE1-Aβ cycle. The activation of EPAC-Rap1 pathway was involved in the inhibition of miR-124 in hippocampus under hypoxia or Aβ insult. Our data suggest that, as an endogenous regulator of BACE1 protein, miR-124 may play a role in AD onset induced by CCH.
authors.affiliation: Department of Pathology, Capital Medical University, 10 Xi Tou Tiao, You An Men Street, Beijing, 100069, People's Republic of China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Capital Medical University, 10 Xi Tou Tiao, You An Men Street, Beijing, 100069, People's Republic of China.
authors.forename: Xiongweiye
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Pathology, Capital Medical University, 10 Xi Tou Tiao, You An Men Street, Beijing, 100069, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Fang
authors.affiliation: Department of Pathology, Capital Medical University, 10 Xi Tou Tiao, You An Men Street, Beijing, 100069, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pathology, Capital Medical University, 10 Xi Tou Tiao, You An Men Street, Beijing, 100069, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Pathology, Capital Medical University, 10 Xi Tou Tiao, You An Men Street, Beijing, 100069, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pathology, Capital Medical University, 10 Xi Tou Tiao, You An Men Street, Beijing, 100069, People's Republic of China. liliang8698@yeah.net.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000235:genetics* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics* / Q000378:metabolism; D002545:Brain Ischemia / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002908:Chronic Disease; D015536:Down-Regulation / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D020662:Guanine Nucleotide Exchange Factors; C509207:MIRN124 microRNA, human; C548144:MIRN124 microRNA, rat; D035683:MicroRNAs; C526973:Rapgef3 protein, rat; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509281:Bace1 protein, rat; D020827:rap1 GTP-Binding Proteins
keywords: Alzheimer’s disease; Amyloid-β; Chronic cerebral hypoperfusion; MicroRNA-124; β-Site amyloid precursor protein cleaving enzyme 1