The Potential Role of Hypoxia-inducible Factor-1 in the Progression and Therapy of Central Nervous System Diseases

Author:

Chen Hongxiu1,Ma Di2,Yue Feixue2,Qi Yajie2,Dou Manman2,Cui Liuping2,Xing Yingqi1

Affiliation:

1. Department of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, China

2. Department of Neurology, The First Hospital of Jilin University, Changchun, China

Abstract

: Hypoxia-inducible factor-1 (HIF-1) is a heterodimer protein composed of an oxygen-regulated functional subunit, HIF-1α, and a structural subunit, HIF-1β, belonging to the basic helix-loop-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 broad spectrum of target genes involved in glucose metabolism, angiogenesis, and erythropoiesis to generate the adaptive response to avoid or 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. It presents robust evidence that HIF-1 may represent a potential therapeutic target for CNS-related diseases.

Publisher

Bentham Science Publishers Ltd.

Subject

Pharmacology (medical),Psychiatry and Mental health,Neurology (clinical),Neurology,Pharmacology,General Medicine

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