Association of lectin-like oxidized low density lipoprotein receptor 1 (OLR1) polymorphisms with late-onset Alzheimer disease in Han Chinese

Wang, Zuo-Teng; Zhong, Xiaoling; Tan, Meng-Shan; Wang, Hui-Fu; Tan, Cheng; Zhang, Wei; Zheng, Zhan-Jie; Kong, Lingli; Tan, Lan; Sun, Li

doi:10.21037/atm.2018.04.31

Cited by 7 publications

(5 citation statements)

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“…BP GO analysis also identified Olr1 as an inflammatory and immune system response gene. Several studies suggest a role for Olr1 in lipid metabolism, and genetic variation in Olr1 as a risk factor for AD [22][23][24], but little is known about Olr1 in AD-associated neuroinflammation. Furthermore, Olr1 was recognized as a gene involved in the phagosome pathway by KEGG, suggesting an important role in multiple AD pathogenic processes.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional response of murine microglia in Alzheimer’s disease and inflammation

2022

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Background Alzheimer’s disease (AD) is a neurodegenerative disorder and is the most common cause of late-onset dementia. Microglia, the primary innate immune cells of the central nervous system (CNS), have a complex role in AD neuropathology. In the initial stages of AD, microglia play a role in limiting pathology by removing amyloid-β (Aβ) by phagocytosis. In contrast, microglia also release pro-inflammatory cytokines and chemokines to promote neuroinflammation and exacerbate AD neuropathology. Therefore, investigating microglial gene networks could identify new targets for therapeutic strategies for AD. Results We identified 465 differentially expressed genes (DEG) in 5XFAD versus wild-type mice by microarray, 354 DEG in lipopolysaccharide (LPS)-stimulated N9 microglia versus unstimulated control cells using RNA-sequencing (RNA-seq), with 32 DEG common between both datasets. Analyses of the 32 common DEG uncovered numerous molecular functions and pathways involved in Aβ phagocytosis and neuroinflammation associated with AD. Furthermore, multiplex ELISA confirmed the induction of several cytokines and chemokines in LPS-stimulated microglia. Conclusions In summary, AD triggered multiple signaling pathways that regulate numerous genes in microglia, contributing to Aβ phagocytosis and neuroinflammation. Overall, these data identified several regulatory factors and biomarkers in microglia that could be useful in further understanding AD neuropathology.

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Section: Discussionmentioning

confidence: 99%

Transcriptional response of murine microglia in Alzheimer’s disease and inflammation

2022

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“…Compelling evidence has shown the transport of Aβ by serum albumin and apolipoproteins in the blood plasma, , likely due to the poor solubility of the peptide as well as the chaperone-like capacity of serum albumin − against the conformational changes of Aβ. Furthermore, while specific receptors on microglia and monocytes/macrophages in the brain may determine the clearance of extracellular Aβ peptides through noninflammatory phagocytosis or pro-inflammatory cytokine secretion, − adherence of complement C3b to complement receptor 1 (CR1) of erythrocytes is a mechanism hypothesized for the peripheral clearance of Aβ …”

Section: Introductionmentioning

confidence: 99%

Differential Roles of Plasma Protein Corona on Immune Cell Association and Cytokine Secretion of Oligomeric and Fibrillar Beta-Amyloid

et al. 2019

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Alzheimer’s disease (AD) is a primary neurological disease with no effective cure. A hallmark of AD is the presence of intracellular tangles and extracellular plaques derived from the aberrant aggregation of tau- and beta-amyloid (Aβ). Aβ presents in the brain as well as in cerebrospinal fluid and the circulation, and Aβ toxicity has been attributed to amyloidosis and inflammation, among other causes. In this study, the effects of the plasma protein corona have been investigated with regard to the blood cell association and cytokine secretion of oligomeric (Aβo) and fibrillar Aβ1–42(Aβf), two major forms of the peptide aggregates. Aβo displayed little change in membrane association in whole blood or washed blood (i.e., cells in the absence of plasma proteins) at 37 °C, while Aβf showed a clear preference for binding with all cell types sans plasma proteins. Immune cells exposed to Aβo, but not to Aβf, resulted in significant expression of cytokines IL-6 and TNF measured in real-time by a localized surface plasmon resonance sensor. These observations indicate greater immune cell association and cytokine stimulation of Aβo than Aβf and shed new light on the contrasting toxicities of Aβo and Aβf resulting from their differential capacities in acquiring a plasma protein corona. These results further implicate a close connection between Aβ amyloidosis and immunopathology in AD.

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“…De fato, a literatura epidemiológica e clínica tem relatado uma associação entre aterosclerose, fatores de risco vascular e DA. Portanto, é possível que variações no ORL1 possam levar a uma menor eficiência na remoção de LDL oxidado e, assim, ao aumento do peptídeo beta-amiloide, podendo resultar na morte de neurônios 37 .…”

Section: Resultsunclassified

Receptores neurais e a doença de Alzheimer: uma revisão sistemática da literatura sobre as famílias de receptores mais associadas a doença, suas funções e áreas de expressão

Câmara

2019

J. bras. psiquiatr.

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RESUMO Objetivo O artigo tem como objetivo determinar as famílias de receptores mais estudadas, envolvidas com a doença de Alzheimer, assim como determinar a região do sistema nervoso na qual mais tipos de receptores são expressos e quais funções dos receptores estão predominantemente associadas com a patologia em questão. O artigo busca mostrar os modelos e métodos mais utilizados nessas pesquisas, resumindo alguns achados e discutindo o impacto desses estudos no conhecimento científico. Métodos Esta revisão utilizou-se de uma metodologia sistemática (Prospero; ID 141957). Resultados Pode-se constatar que os receptores de transcrição nuclear foram os mais estudados. A maior parte desses receptores se expressa no córtex cerebral e hipocampo. Adicionalmente, a maioria das pesquisas avaliou os receptores relacionados com os efeitos benéficos na doença. A eliminação da proteína amiloide ou o bloqueio de vias relacionadas à síntese dessa proteína foram as principais funções desempenhadas por esses receptores. Por fim, as técnicas de imunoistoquímica e reação em cadeia de polimerase em tempo real (RT-PCR), respectivamente, foram as mais utilizadas, e os roedores consistiram no principal modelo de estudo. Conclusões Os receptores de transcrição nuclear, o córtex cerebral, o hipocampo, a micróglia e a proteína beta-amiloide mostraram importância na patogênese da doença de Alzheimer neste estudo.

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Association of lectin-like oxidized low density lipoprotein receptor 1 (OLR1) polymorphisms with late-onset Alzheimer disease in Han Chinese

Abstract: Our study showed that the SNPs (rs1050283, rs1050286, rs17808009) located in the 3'UTR of OLR1 may not involve in the mechanism of LOAD in Han Chinese population.

Cited by 7 publications

References 62 publications

Transcriptional response of murine microglia in Alzheimer’s disease and inflammation

Transcriptional response of murine microglia in Alzheimer’s disease and inflammation

Differential Roles of Plasma Protein Corona on Immune Cell Association and Cytokine Secretion of Oligomeric and Fibrillar Beta-Amyloid

Receptores neurais e a doença de Alzheimer: uma revisão sistemática da literatura sobre as famílias de receptores mais associadas a doença, suas funções e áreas de expressão

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