microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain

Kim, Jae Kwang; Yoon, Hyuk; Horie, Takahiro; Burchett, Jack M.; Restivo, Jessica L.; Rotllan, Noemí; Ramírez, Cristina M.; Verghese, Philip B.; Ihara, Masafumi; Hoe, Hyang Sook; Esau, Christine; Fernández‐Hernando, Carlos; Holtzman, David M.; Cirrito, John R.; Ono, Koh; Kim, Jung-Su

doi:10.1523/jneurosci.2053-15.2015

Cited by 108 publications

(79 citation statements)

References 41 publications

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“…After 48 hours, the levels of miR-155, miR-233, and miR-33 were upregulated and miR-433 was downregulated in response to Ab (represented by solid lines). The targeted genes of the miRNAs and their involved pathways (represented by dashed lines) were supported by the following studies: 1) Xu et al 47 ; 2) Lukiw et al 46 ; 3) Qadir et al 48 ; 4) Kim et al 19 These target genes were confirmed in the neuroretina or RPE/choroid with same tendency in our study. IV, intravitreal injection.…”

Section: Discussionsupporting

confidence: 89%

“…It has been clearly reported that miR-33 regulates ABCA1 and Ab levels in the brain. 19 MicroR-33 could reduce the expression of the ABCA1 gene by binding to the 3 0 UTR of ABCA1. ABCA1 has a positive effect on ApoE lipidation and an inhibitory effect on Ab levels.…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNAs (miRNAs) have emerged as a new therapeutic direction for several diseases, 19 including neurodegenerative disorders. 20 MicroRNAs are single-stranded short (21)(22)(23) nucleotides long) noncoding RNAs that are involved in posttranscriptional modulation.…”

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confidence: 99%

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MicroRNA Expression Patterns Involved in Amyloid Beta–Induced Retinal Degeneration

Huang

Sun

Wang

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Huang P, Sun J, Wang F, et al. MicroRNA expression patterns involved in amyloid beta-induced retinal degeneration. Invest Ophthalmol Vis Sci. 2017;58:172658: -173558: . DOI: 10.1167 PURPOSE. Dry age-related macular degeneration (AMD) is characterized by the accumulation of drusen under Bruch's membrane, and amyloid beta (Ab) is speculated to be one of the key pathologic factors. While the detrimental effects of Ab on retinas have been widely explored, Ab-induced epigenetic regulatory changes have yet to be fully investigated. We therefore aimed to identify the microRNA (miRNA) expression profiles in an Ab-induced mouse model of retinal degeneration.METHODS. C57BL/6 mice were intravitreally injected with Ab 1-40 or PBS and the eye tissues were collected for hematoxylin and eosin (H&E) staining, apoptosis immunofluorescence staining, and miRNA profiling. After filtering, 10 miRNAs and their target genes were chosen for quantitative RT-PCR (qRT-PCR) confirmations. Pathway analyses were employed for further bioinformatic analyses.RESULTS. Hematoxylin and eosin-stained sections of retinal pigment epithelium (RPE)/neural retina tissue demonstrated degenerative alterations, and immunofluorescence testing revealed apoptosis within the retina after Ab treatments. MicroRNA profiling revealed 61 miRNAs that were differentially expressed between the model and the control group. Among these, 38 miRNAs were upregulated (fold change > 1.5, P < 0.05) and 23 miRNAs were downregulated (fold change < 0.667, P < 0.05). Five of the 10 selected miRNAs (miR-142, miR-216, miR-155, miR-223, and miR-433) as well as several key target genes (CFH, IGF-1R, c-MET, and ABCA1) were confirmed by qRT-PCR analyses.CONCLUSIONS. Our study is the first to profile the miRNA expression patterns and suggests that Ab accumulation could lead to relevant biochemical alternations such as complement activation, barrier impairment, apoptosis, and positive feedback of Ab production.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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MicroRNA Expression Patterns Involved in Amyloid Beta–Induced Retinal Degeneration

Huang

Sun

Wang

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Treatment with the RXR agonist bexarotene also improves Aβ clearance and cognition [106], in a manner dependent on the presence of both APOE [106] and ABCA1 [107]. Other treatments to improve apoE4 lipidation (e.g., microRNA-33 induction [108], retinoic acid [109]) could prove useful in preventing brain phenotypes associated with APOE4 and neurodegeneration.…”

Section: Mechanisms Of Effects Of Apoe Genotype Effectsmentioning

confidence: 99%

Alzheimer's Disease Genetic Risk Factor APOE-ε4 Also Affects Normal Brain Function

Battista¹,

Heinsinger²,

Rebeck³

2016

CAR

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APOE-ε4 is the strongest genetic risk factor for Alzheimer’s disease (AD), and is associated with an increase in the levels of amyloid deposition and an early age of onset. Recent data demonstrate that AD pathological changes occur decades before clinical symptoms, raising questions about the precise onset of the disease. Now a convergence of approaches in mice and humans has demonstrated that APOE-ε4 affects normal brain function even very early in life in the absence of gross AD pathological changes. Normal mice expressing APOE4 have task-specific spatial learning deficits, as well as reduced NMDAR-dependent signaling and structural changes to presynaptic and postsynaptic compartments in neurons, particularly in hippocampal regions. Young humans possessing APOE-ε4 are more adept than APOE-ε4 negative individuals at some behavioral tasks, and functional magnetic resonance imaging has shown that inheritance of APOE-ε4 has specific effects on medial temporal brain activities. These findings suggest that inheritance of APOE-ε4 causes life long changes to the brain that may be related to the late risk of AD. Several possible mechanisms of how APOE-ε4 could affect brain neurochemistry, structure, and function are reviewed.

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“…to dementia, the presence of the APOE ε4 allele is associated with more rapid brain volume deficits and cortical thinning over time, as shown in several longitudinal MRI studies (85)(86)(87).…”

Section: Discussionmentioning

confidence: 83%

Padrões de atrofia cortical e declínio cognitivo associado ao envelhecimento saudável: um estudo de seguimento por ressonância magnética estrutural

Silveira¹

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microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain

Abstract: Dysregulation of amyloid-␤ (A␤) metabolism is critical for

Cited by 108 publications

References 41 publications

MicroRNA Expression Patterns Involved in Amyloid Beta–Induced Retinal Degeneration

MicroRNA Expression Patterns Involved in Amyloid Beta–Induced Retinal Degeneration

Alzheimer's Disease Genetic Risk Factor APOE-ε4 Also Affects Normal Brain Function

Padrões de atrofia cortical e declínio cognitivo associado ao envelhecimento saudável: um estudo de seguimento por ressonância magnética estrutural

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