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帕金森病中的缺氧途径:从发病机制到治疗靶点。

Hypoxia Pathways in Parkinson's Disease: From Pathogenesis to Therapeutic Targets.

机构信息

National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.

Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Int J Mol Sci. 2024 Sep 29;25(19):10484. doi: 10.3390/ijms251910484.

Abstract

The human brain is highly dependent on oxygen, utilizing approximately 20% of the body's oxygen at rest. Oxygen deprivation to the brain can lead to loss of consciousness within seconds and death within minutes. Recent studies have identified regions of the brain with spontaneous episodic hypoxia, referred to as "hypoxic pockets". Hypoxia can also result from impaired blood flow due to conditions such as heart disease, blood clots, stroke, or hemorrhage, as well as from reduced oxygen intake or excessive oxygen consumption caused by factors like low ambient oxygen, pulmonary diseases, infections, inflammation, and cancer. Severe hypoxia in the brain can manifest symptoms similar to Parkinson's disease (PD), including cerebral edema, mood disturbances, and cognitive impairments. Additionally, the development of PD appears to be closely associated with hypoxia and hypoxic pathways. This review seeks to investigate the molecular interactions between hypoxia and PD, emphasizing the pathological role of hypoxic pathways in PD and exploring their potential as therapeutic targets.

摘要

人脑对氧气高度依赖,在休息时大约消耗身体氧气的 20%。大脑缺氧会导致几秒钟内失去意识,几分钟内死亡。最近的研究已经确定了大脑中存在自发性间歇性缺氧的区域,称为“缺氧口袋”。由于心脏病、血栓、中风或出血等原因导致血流受损,以及由于低环境氧气、肺部疾病、感染、炎症和癌症等因素导致氧气摄入减少或氧气消耗过多,也会导致缺氧。大脑严重缺氧会表现出类似于帕金森病(PD)的症状,包括脑水肿、情绪障碍和认知障碍。此外,PD 的发展似乎与缺氧和缺氧途径密切相关。本综述旨在探讨缺氧与 PD 之间的分子相互作用,强调缺氧途径在 PD 中的病理作用,并探索它们作为治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07fe/11477385/b509eb9dd903/ijms-25-10484-g001.jpg

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