Abstract:
:BACE1 is the rate-limiting enzyme for amyloid-β peptides (Aβ) generation, a key event in the pathogenesis of Alzheimer's disease (AD). By an unknown mechanism, levels of BACE1 and a BACE1 mRNA-stabilizing antisense RNA (BACE1-AS) are elevated in the brains of AD patients, implicating that dysregulation of BACE1 expression plays an important role in AD pathogenesis. We found that nuclear factor erythroid-derived 2-related factor 2 (NRF2/NFE2L2) represses the expression of BACE1 and BACE1-AS through binding to antioxidant response elements (AREs) in their promoters of mouse and human. NRF2-mediated inhibition of BACE1 and BACE1-AS expression is independent of redox regulation. NRF2 activation decreases production of BACE1 and BACE1-AS transcripts and Aβ production and ameliorates cognitive deficits in animal models of AD. Depletion of NRF2 increases BACE1 and BACE1-AS expression and Aβ production and worsens cognitive deficits. Our findings suggest that activation of NRF2 can prevent a key early pathogenic process in AD.
journal_name
Proc Natl Acad Sci U S Aauthors
Bahn G,Park JS,Yun UJ,Lee YJ,Choi Y,Park JS,Baek SH,Choi BY,Cho YS,Kim HK,Han J,Sul JH,Baik SH,Lim J,Wakabayashi N,Bae SH,Han JW,Arumugam TV,Mattson MP,Jo DGdoi
10.1073/pnas.1819541116subject
Has Abstractpub_date
2019-06-18 00:00:00pages
12516-12523issue
25eissn
0027-8424issn
1091-6490pii
1819541116journal_volume
116pub_type
杂志文章abstract::We have developed a cell-free system to study bacteriophage lambda DNA replication. Maximal DNA synthesis in vitro requires the four deoxynucleoside triphosphates, ATP, and exogenous lambda DNA. DNA synthesis requires the products of the phage O and P genes but is not inhibited by lambda repressor. The kinetics of syn...
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