β-Secretase (BACE) and GSK-3 mRNA levels in Alzheimer’s disease

Preece, Paul; Virley, David; Costandi, Moheb; Coombes, Robert; Moss, Stephen J.; Mudge, Anne W.; Jazin, Elena; Cairns, Nigel J.

doi:10.1016/s0169-328x(03)00233-x

Cited by 55 publications

(39 citation statements)

References 34 publications

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“…Edge-type swim tracing was recorded in 2VO rats, which was reversed by lenti-pre-miR-195. reduced in the AD and/or aging brains (Harrison et al, 1994;Preece et al, 2003). In contrast, we found, in the present study, that the level of APP mRNA was unchanged whereas BACE1 mRNA was decreased.…”

Section: Vo Produces Deposition Of A␤ Association With Downregulatiocontrasting

confidence: 82%

MicroRNA-195Protects Against Dementia Induced by Chronic Brain Hypoperfusion via Its Anti-Amyloidogenic Effect in Rats

et al. 2013

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Previous studies have demonstrated that chronic brain hypoperfusion (CBH) causes A␤ aggregation by upregulating expression of amyloid precursor protein (APP) and ␤-site APP cleaving enzyme 1 (BACE1) protein, which is accompanied by cognitive impairment, but the mechanisms are not fully understood. In this study, we evaluated the effect of microRNA on memory impairment in rats induced by CBH. We show here that CBH generated by bilateral common carotid artery occlusion (2VO) significantly decreased the learning and memory ability in rats, as assessed by Morris water maze, and upregulated expression of APP and BACE1 proteins in the hippocampus and cortex of rats, as evaluated by Western blot and immunofluorescence. In reciprocal, qRT-PCR analysis showed that microRNA-195 (miR-195) was downregulated in both the hippocampus and cortex of rats following CBH, and in the plasma of dementia patients. APP and BACE1 proteins were downregulated by miR-195 overexpression, upregulated by miR-195 inhibition, and unchanged by binding-site mutation or miR-masks, indicating that APP and BACE1 are two potential targets for miR-195. Knockdown of endogenous miR-195 by lentiviral vector-mediated overexpression of its antisense molecule (lenti-pre-AMO-miR-195) elicited dementia in rats, whereas overexpression of miR-195 using lenti-pre-miR-195 reduced dementia vulnerability triggered by 2VO. Additionally, chromatin immunoprecipitation analysis showed that NFB was bound to the promoter region of miR-195 and inhibited its expression. We conclude that miR-195 may play a key role in determining dementia susceptibility in 2VO rats by regulating APP and BACE1 expression at the post-transcriptional level, and exogenous complement of miR-195 may be a potentially valuable anti-dementia approach.

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Section: Vo Produces Deposition Of A␤ Association With Downregulatiocontrasting

confidence: 82%

MicroRNA-195Protects Against Dementia Induced by Chronic Brain Hypoperfusion via Its Anti-Amyloidogenic Effect in Rats

et al. 2013

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“…Although BACE is known to play a key role in the production of Ab in the amyloidogenic pathway of AD [16], studies on BACE in patients with AD show different results. Fukumoto et al [17] reported that the activity and expression of BACE increase in the brain tissue of AD patients, however, other authors reported that there is no difference in the expression of BACE and BACE mRNA between the groups with AD and control [18,19]. Thus, in order to examine the relation between ischemic neuronal insults and BACE, we measured the expression of BACE and BACE mRNA and the activity of BACE following ischemic insults of varying duration of.…”

Section: Discussionmentioning

confidence: 98%

Effect of Ischemic Neuronal Insults on Amyloid Precursor Protein Processing

et al. 2006

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The nature of the association between ischemic stroke and Alzheimer's disease (AD) at the cellular and molecular level is still unknown. We evaluated the effect of ischemic neuronal insults on the regulation of amyloid precursor protein (APP) processing. We used an in vitro model of cerebral ischemia (oxygen-glucose deprivation) to evaluate the effect of ischemic neuronal insults on the amyloidogenic and non-amyloidogenic pathways using human neuroblastoma cell line and primary cultured cells of transgenic mice which expressed human APP (Tg2576). Ischemic neuronal insults increased the production of Ab in Tg2576 primary culture cells compared to controls. A disintegrin and metalloprotease 10 (ADAM 10) was markedly increased in early stage of ischemic insults, which was followed by decreased level of ADAM 10 expression in later stage. The protein and mRNA expression of b-site cleavage enzyme (BACE) and BACE activity was not significantly different between the group of ischemic insults and control. By contrast, the activity of c-secretase was significantly increased after 4 h of ischemic insults, as compared to controls. The present study showed that the ischemic neuronal insults increased the production of Ab by influencing APP metabolism, which may link the role of ischemic insults to the pathogenesis of AD.

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“…Indeed, post-mortem analysis revealed a 2.7-fold increase in BACE1 protein expression in the cerebral cortex of patients suffering of AD, in parallel with a similar increase in A␤ peptide levels, when compared with age-matched controls (31). Intriguingly, the up-regulated BACE1 protein expression (31)(32)(33) and activity (32,33), which were correlated (33), could not be transposed to the level of mRNA; in AD brains, BACE1 mRNA levels remain unchanged (31,40,41).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-298 and MicroRNA-328 Regulate Expression of Mouse β-Amyloid Precursor Protein-converting Enzyme 1

Boissonneault

Plante

Rivest

et al. 2009

Journal of Biological Chemistry

294

223

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MicroRNAs (miRNAs) are key regulatory RNAs known to repress mRNA translation through recognition of specific binding sites located mainly in their 3-untranslated region (UTR). Loss of specific miRNA control of gene expression is thus expected to underlie serious genetic diseases. Intriguingly, previous post-mortem analyses showed higher ␤-amyloid precursor protein-converting enzyme (BACE) protein, but not mRNA, levels in the brain of patients that suffered from Alzheimer disease (AD). Here we also observed a loss of correlation between BACE1 mRNA and protein levels in the hippocampus of a mouse model of AD. Consistent with an impairment of miRNAmediated regulation of BACE1 expression, these findings prompted us to investigate the regulatory role of the BACE1 3-UTR element and the possible involvement of specific miRNAs in cultured neuronal (N2a) and fibroblastic (NIH 3T3) cells. Through various experimental approaches, we validated computational predictions and demonstrated that miR-298 and miR-328 recognize specific binding sites in the 3-UTR of BACE1 mRNA and exert regulatory effects on BACE1 protein expression in cultured neuronal cells. Our results may provide the molecular basis underlying BACE1 deregulation in AD and offer new perspectives on the etiology of this neurological disorder.

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β-Secretase (BACE) and GSK-3 mRNA levels in Alzheimer’s disease

Cited by 55 publications

References 34 publications

MicroRNA-195Protects Against Dementia Induced by Chronic Brain Hypoperfusion via Its Anti-Amyloidogenic Effect in Rats

MicroRNA-195Protects Against Dementia Induced by Chronic Brain Hypoperfusion via Its Anti-Amyloidogenic Effect in Rats

Effect of Ischemic Neuronal Insults on Amyloid Precursor Protein Processing

MicroRNA-298 and MicroRNA-328 Regulate Expression of Mouse β-Amyloid Precursor Protein-converting Enzyme 1

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