Scholarlink

<p>Chronic cerebral hypoperfusion (CCH) is a critical indicator of cognitive impairment and dementia, especially vascular dementia. Cerebral blood flow disturbance alters the properties of neurons and glial cells as a result of a deficit in energy sources. Hypoxia-inducible factor 1 alpha (HIF- 1α) is a transcription factor that controls gene activity in response to low oxygen levels. It regulates a complex network of cellular adaptations to improve oxygenation, metabolic reprogramming, and cell survival in hypoxic situations. However, recent research suggests that HIF- 1α plays a role not only in neuroprotection but also in brain injury. It is therefore critical to fully comprehend the mechanisms behind these disorders. This review highlights the dual role of HIF- 1α in CCH-induced VaD. Initially, HIF- 1α provides a neuroprotection by promoting angiogenesis through vascular endothelial growth factor (VEGF) signaling. However, prolonged activation can detrimentally effects, including oxidative stress, neuroinflammation, blood–brain barrier dysfunction, and cognitive impairment. Evidence suggests that HIF- 1α exerts its protective effects in acute ischemic/hypoxic-induced VaD through pathways such as PI3 K/AKT/mTOR and MAPK/p–c-Jun signaling. However, its dysregulation in chronic stages of CCH contributes to cognitive decline and disease progression. Understanding the complex role of HIF- 1α and its interactions with other molecular pathways is crucial for developing effective therapeutic strategies. Therefore, an informed, in-depth discussion of its involvement in these pathologic processes is necessary, as a precise contribution of HIF- 1α to CCH-induced VaD remains to be established and requires further investigation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

The Bidirectional Role of Hypoxia-Inducible Factor 1 Alpha in Vascular Dementia Caused by Chronic Cerebral Hypoperfusion

  • 期刊论文

  • 发表日期：

    2025年4月9日

查看全文
  • Phakkawat Thangwong,
  • Chainarong Tocharus,
  • Jiraporn Tocharus

摘要

Chronic cerebral hypoperfusion (CCH) is a critical indicator of cognitive impairment and dementia, especially vascular dementia. Cerebral blood flow disturbance alters the properties of neurons and glial cells as a result of a deficit in energy sources. Hypoxia-inducible factor 1 alpha (HIF- 1α) is a transcription factor that controls gene activity in response to low oxygen levels. It regulates a complex network of cellular adaptations to improve oxygenation, metabolic reprogramming, and cell survival in hypoxic situations. However, recent research suggests that HIF- 1α plays a role not only in neuroprotection but also in brain injury. It is therefore critical to fully comprehend the mechanisms behind these disorders. This review highlights the dual role of HIF- 1α in CCH-induced VaD. Initially, HIF- 1α provides a neuroprotection by promoting angiogenesis through vascular endothelial growth factor (VEGF) signaling. However, prolonged activation can detrimentally effects, including oxidative stress, neuroinflammation, blood–brain barrier dysfunction, and cognitive impairment. Evidence suggests that HIF- 1α exerts its protective effects in acute ischemic/hypoxic-induced VaD through pathways such as PI3 K/AKT/mTOR and MAPK/p–c-Jun signaling. However, its dysregulation in chronic stages of CCH contributes to cognitive decline and disease progression. Understanding the complex role of HIF- 1α and its interactions with other molecular pathways is crucial for developing effective therapeutic strategies. Therefore, an informed, in-depth discussion of its involvement in these pathologic processes is necessary, as a precise contribution of HIF- 1α to CCH-induced VaD remains to be established and requires further investigation.