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1.
Curr Neuropharmacol ; 20(9): 1651-1666, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34325641

RESUMO

Hypoxia-inducible factor-1 (HIF-1) is a heterodimer protein composed of an oxygenregulated functional subunit, HIF-1α, and a structural subunit, HIF-1ß, belonging to the basic helixloop- helix family. Strict regulation of HIF-1 protein stability and subsequent transcriptional activity involves various molecular interactions and is primarily controlled by post-transcriptional modifications. Hypoxia, owing to impaired cerebral blood flow, has been implicated in a range of central nervous system (CNS) diseases by exerting a deleterious effect on brain function. As a master oxygen- sensitive transcription regulator, HIF-1 is responsible for upregulating a wide spectrum of target genes involved in glucose metabolism, angiogenesis, and erythropoiesis to generate the adaptive response to avoid, or at least minimize, hypoxic brain injury. However, prolonged, severe oxygen deprivation may directly contribute to the role-conversion of HIF-1, namely, from neuroprotection to the promotion of cell death. Currently, an increasing number of studies support the fact HIF-1 is involved in a variety of CNS-related diseases, such as intracranial atherosclerosis, stroke, and neurodegenerative diseases. This review article chiefly focuses on the effect of HIF-1 on the pathogenesis and mechanism of progression of numerous CNS-related disorders by mediating the expression of various downstream genes and extensive biological functional events and presents robust evidence that HIF-1 may represent a potential therapeutic target for CNS-related diseases.


Assuntos
Doenças do Sistema Nervoso Central , Fator 1 Induzível por Hipóxia , Hipóxia Celular/fisiologia , Doenças do Sistema Nervoso Central/terapia , Humanos , Hipóxia/metabolismo , Fator 1 Induzível por Hipóxia/metabolismo , Oxigênio/metabolismo
2.
Biomed Res Int ; 2020: 4749135, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733941

RESUMO

Cardiovascular and cerebrovascular diseases caused by atherosclerosis have a high disability rate and reduce the quality of life of the population. Therefore, understanding the mechanism of atherosclerosis and its control may interfere with the progression of atherosclerosis and thus control the occurrence of diseases closely related to atherosclerosis. TSP-1 is a factor that has been found to have an antiangiogenic effect, and CD47, as the receptor of TSP-1, can participate in the regulation of antiangiogenesis of atherosclerosis. VEGF is an important regulator of angiogenesis, and TSP-1/CD47 can cause VEGF and its downstream expression. Therefore, the TSP-1/CD47/VEGF/VEGFR2 signal may have an important influence on atherosclerosis. In addition, some inflammatory factors, such as IL-1 and NLRP3, can also affect atherosclerosis. This review will be expounded focusing on the pathogenesis and influencing factors of atherosclerosis.


Assuntos
Antígeno CD47/metabolismo , Transdução de Sinais , Doenças Vasculares/metabolismo , Animais , Citocinas/metabolismo , Humanos , Inflamação/patologia , Terapia de Alvo Molecular , Doenças Vasculares/imunologia
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