Epigenetic regulation of BACE1 in Alzheimer’s disease patients and in transgenic mice

Marques, Sueli; Lemos, Raquel; Ferreiro, Elisabete; Martins, Madalena; Mendonça, Alexandre de; Santana, Isabel; Outeiro, Tiago F.; Pereira, Cláudia

doi:10.1016/j.neuroscience.2012.06.029

Cited by 72 publications

(43 citation statements)

References 52 publications

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“…A previous study also demonstrated that miR-29c is reduced in the peripheral blood of patients with AD (17). Increased expression of BACE1 has been previously observed in the brain, CSF and peripheral blood of patients with AD (18,19), suggesting that increased expression of BACE1 is an important risk factor for AD. The present study also revealed, using an ELISA, that the expression of BACE1 was increased in the peripheral blood of patients with AD.…”

Section: Discussionmentioning

confidence: 75%

MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo

Yang

Song

Zhou

et al. 2015

Molecular Medicine Reports

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Abstract. Alzheimer's disease (AD), characterized by β-amyloid deposition and neurodegeneration, is the most common cause of dementia worldwide. Emerging evidence suggests that ectopic expression of micro (mi)RNAs is involved in the pathogenesis of AD. There is increasing evidence that miRNAs expressed in the brain are involved in neuronal development, survival and apoptosis. The expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is regulated by dysregulated miRNAs in the brain. The present study determined the expression levels of the miRNA-29 (miR-29) family in peripheral blood samples of patients with AD and demonstrated a marked decrease in the expression of miR-29c compared with age-matched controls. In addition, a significant increase in the exprssion of BACE1 was observed in the peripheral blood of patients with AD. Correlation analysis revealed that the expression of miR-29c was negatively correlated with the protein expression of BACE1 in the peripheral blood samples from patients with AD. The present study also investigated the role of miR-29 on hippocampal neurons in vitro and in vivo. The results demonstrated that the upregulation of miR-29c promoted learning and memory behaviors in SAMP8 mice, at least partially, by increasing the activity of protein kinase A/cAMP response element-binding protein, involved in neuroprotection. This evidence suggested that miR-29c may be a promising potential therapeutic target against AD.

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Section: Discussionmentioning

confidence: 75%

MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo

Yang

Song

Zhou

et al. 2015

Molecular Medicine Reports

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“…Importantly, this injurious process appears to be preventable in brains of MG − mice, a finding of significant therapeutic import. Whether this involves epigenetic changes or an altered gut microbiome is a critical subject for further inquiry (32,33).…”

Section: Discussionmentioning

confidence: 99%

Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans

Cai

Uribarri²,

Zhu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

139

104

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Age-associated dementia and Alzheimer's disease (AD) are currently epidemic. Neither their cause nor connection to the metabolic syndrome (MS) is clear. Suppression of deacetylase survival factor sirtuin 1 (SIRT1), a key host defense, is a central feature of AD. Age-related MS and diabetes are also causally associated with suppressed SIRT1 partly due to oxidant glycotoxins [advanced glycation end products (AGEs)]. Changes in the modern diet include excessive nutrient-bound AGEs, such as neurotoxic methyl-glyoxal derivatives (MG). To determine whether dietary AGEs promote AD, we evaluated WT mice pair-fed three diets throughout life:, and regular (Reg) chow. Older MG + -fed mice, similar to old Reg controls, developed MS, increased brain amyloid-β 42 , deposits of AGEs, gliosis, and cognitive deficits, accompanied by suppressed SIRT1, nicotinamide phosphoribosyltransferase, AGE receptor 1, and PPARγ. These changes were not due to aging or caloric intake, as neither these changes nor the MS were present in age-matched, pair-fed MG − mice. The mouse data were enhanced by significant temporal correlations between high circulating AGEs and impaired cognition, as well as insulin sensitivity in older humans, in whom dietary and serum MG levels strongly and inversely associated with SIRT1 gene expression. The data identify a specific AGE (MG) as a modifiable risk factor for AD and MS, possibly acting via suppressed SIRT1 and other host defenses, to promote chronic oxidant stress and inflammation. Because SIRT1 deficiency in humans is both preventable and reversible by AGE reduction, a therapeutic strategy that includes AGE reduction may offer a new strategy to combat the epidemics of AD and MS.neural | insulin resistance | obesity | nutrition | caloric restriction

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“…NCSTN expression did not show alterations in AD in a study reported by Marques et al (2012), while BACE1 expression increased . When we studied our independent cohort, we found NCSTN differed from controls and NP, but BACE1 did not (HerreraRivero et al, 2013).…”

Section: Discussionmentioning

confidence: 57%

A strategy focused on MAPT, APP, NCSTN and BACE1 to build blood classifiers for Alzheimer׳s disease

Herrera-Rivero

Hernández-Aguilar

Aranda-Abreu

2015

Journal of Theoretical Biology

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Epigenetic regulation of BACE1 in Alzheimer’s disease patients and in transgenic mice

Cited by 72 publications

References 52 publications

MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo

MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo

Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans

A strategy focused on MAPT, APP, NCSTN and BACE1 to build blood classifiers for Alzheimer׳s disease

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