Abstract：
:Tau pathologically aggregates in Alzheimer's disease, and evidence suggests that reducing tau expression may be safe and beneficial for the prevention or treatment of this disease. We sought to examine the role of the 3'-untranslated region (3'-UTR) of human tau mRNA in regulating tau expression. Tau expresses two 3'-UTR isoforms, long and short, as a result of alternative polyadenylation. Using luciferase reporter constructs, we found that expression from these isoforms is differentially controlled in human neuroblastoma cell lines M17D and SH-SY5Y. Several microRNAs were computationally identified as candidates that might bind the long, but not short, tau 3'-UTR isoform. A hit from a screen of candidates, miR-34a, was subsequently shown to repress the expression of endogenous tau protein in M17D cells. Conversely, inhibition of endogenously expressed miR-34 family members leads to increased endogenous tau expression. In addition, through an unbiased screen of fragments of the human tau 3'-UTR using a luciferase reporter assay, we identified several other regions in the long tau 3'-UTR isoform that contain regulatory cis-elements. Improved understanding of the regulation of tau expression by its 3'-UTR may ultimately lead to the development of novel therapeutic strategies for the treatment of Alzheimer's disease and other tauopathies. mRNA 3'-untranslated regions (3'-UTR) often regulate transcript stability or translation. Despite the centrality of the tau protein in Alzheimer's and other neurodegenerative diseases, the human tau 3'-UTR has been little studied. This report identifies regions of the tau 3'-UTR that influence expression and shows that microRNA (miR)-34a targets this 3'-UTR to lower expression, which is considered an important therapeutic goal.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Dickson JR,Kruse C,Montagna DR,Finsen B,Wolfe MSdoi
10.1111/jnc.12437subject
Has Abstractpub_date
2013-12-01 00:00:00pages
739-49issue
6eissn
0022-3042issn
1471-4159journal_volume
127pub_type
杂志文章abstract：:While it has been reported that familial Alzheimer's disease (FAD)-linked mutants of amyloid precursor protein (APP) and presenilin (PS)2 induce neuronal cytotoxicity in a manner sensitive to antioxidant and pertussis toxin (PTX), little of the mechanism for PS1-mediated neuronal cell death has been characterized. We ...
journal_title：Journal of neurochemistry
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更新日期：1995-12-01 00:00:00
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doi：10.1111/j.1471-4159.1986.tb04526.x
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.70030914.x
更新日期：1998-03-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.65010268.x
更新日期：1995-07-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1991.tb08172.x
更新日期：1991-02-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1999.0722099.x
更新日期：1999-05-01 00:00:00
abstract：:Modulation of acetylcholine (ACh) release from superfused hippocampal slices was examined when the release of ACh was stimulated by exposure of slices to elevated K+ concentration. Evoked release was not sensitive to inhibition by 0.1 microM tetrodotoxin, but it could be inhibited in a dose-dependent manner by a musca...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb05799.x
更新日期：1990-12-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04655.x
更新日期：2007-08-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.15124
更新日期：2020-07-12 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1993.tb03212.x
更新日期：1993-02-01 00:00:00
abstract：:The functions of the antiapoptotic proteins Bcl-2 and Bcl-xL were examined in glioblastoma cells. Expression of both Bcl-2 and Bcl-xL were found to be elevated in protein lysates from seven early passage cell lines derived from human glioblastoma tumors compared with non-neoplastic glial cells. Down-regulation of both...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.01522.x
更新日期：2003-01-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb07964.x
更新日期：1982-09-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.14702
更新日期：2019-07-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2010.07102.x
更新日期：2011-01-01 00:00:00
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pub_type： 杂志文章
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2002.00992.x
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abstract：:A targeted neuropharmacological, (1)H/(13)C NMR spectroscopy and multivariate statistical approach was used to examine the effects of exogenous GABA and ligands at the GABA(A) receptor family on brain metabolism in the Guinea pig cortical tissue slice. All ligands at GABA(A) receptors generated metabolic patterns whic...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2008.05742.x
更新日期：2009-01-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13085
更新日期：2015-05-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1991.tb06359.x
更新日期：1991-11-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13048
更新日期：2015-04-01 00:00:00
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pub_type： 杂志文章
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更新日期：1999-08-01 00:00:00
abstract：:The specific binding of [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([ 3H]8-OH-DPAT) to 5-hydroxytryptamine (5-HT)-related sites was investigated in several regions of the rat brain. Marked differences were observed in the characteristics of binding to membranes from hippocampus, striatum, and cerebral cortex. Hippocam...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb07155.x
更新日期：1985-06-01 00:00:00
abstract：:EAAC1/EAAT3 is a transporter of glutamate (Glu) present at the post-synaptic neuronal element, in opposition to the two other main transporters, GLAST/EAAT1 and GLT1/EAAT2, expressed at the excitatory amino acid (EAA) synapse by surrounding astrocytes. Although, in the adult, EAAC1/EAAT3 exhibits a rather low expressi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/j.1471-4159.2006.03978.x
更新日期：2006-08-01 00:00:00
abstract：:Abnormalities in the kynurenine pathway may play a role in Huntington's disease (HD). In this study, tryptophan depletion and loading were used to investigate changes in blood kynurenine pathway metabolites, as well as markers of inflammation and oxidative stress in HD patients and healthy controls. Results showed tha...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2005.03070.x
更新日期：2005-05-01 00:00:00
abstract：:The LIM homeobox family of transcription factors is involved in many processes during the development of the mammalian central nerves system. L3, also called Lhx8 (L3/Lhx8), is a recently identified member of the LIM homeobox gene family and is selectively expressed in the medial ganglionic eminence (MGE). Our previou...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2005.03261.x
更新日期：2005-08-01 00:00:00
