Pro-Oxidative and Inflammatory Actions of Extracellular Hemoglobin and Heme: Molecular Events and Implications for Alzheimer's and Parkinson Disease.

IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Biomolecules & Therapeutics Pub Date : 2025-03-01 Epub Date: 2025-02-18 DOI:10.4062/biomolther.2024.224
Nicole Bon Campomayor, Hee Jin Kim, Mikyung Kim
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引用次数: 0

Abstract

Hemoglobin (Hb) and heme, which are typically confined within red blood cells (RBCs), are essential for intravascular transport of gases and nutrients. However, these molecules acquire secondary functions upon exposure to the extracellular environment. Hb and heme generate reactive oxygen species (ROS), which are potent pro-inflammatory agents that contribute to oxidative stress and cellular damage. These events are relevant to neurodegenerative processes, where oxidative stress, irregular deposition of protein aggregates, and chronic inflammation are key pathological features. Extracellular Hb, heme, and oxidative stress derived from hemorrhagic events or RBC lysis may contribute to increased blood-brain barrier (BBB) permeability. These events allow Hb and heme to interact with neuroimmune cells and pathological protein aggregates, further amplifying pro-inflammatory signaling and the progression of Alzheimer's disease (AD) and Parkinson disease (PD). Chronic neuroinflammation, oxidative stress, and mitochondrial dysfunction lead to neuronal degeneration. Here, we sought to elucidate the pro-oxidative and inflammatory actions of extracellular Hb and heme, emphasizing their potential impact on AD and PD development.

细胞外血红蛋白和血红素的促氧化和炎症作用:阿尔茨海默病和帕金森病的分子事件和意义。
血红蛋白(Hb)和血红素通常局限于红细胞(rbc)内,对于气体和营养物质的血管内运输至关重要。然而,这些分子暴露于细胞外环境后获得次要功能。血红蛋白和血红素产生活性氧(ROS),这是一种有效的促炎剂,有助于氧化应激和细胞损伤。这些事件与神经退行性过程有关,其中氧化应激、蛋白质聚集体不规则沉积和慢性炎症是关键的病理特征。细胞外Hb、血红素和氧化应激源自出血事件或红细胞溶解可能有助于增加血脑屏障(BBB)的通透性。这些事件允许Hb和血红素与神经免疫细胞和病理蛋白聚集体相互作用,进一步放大促炎信号和阿尔茨海默病(AD)和帕金森病(PD)的进展。慢性神经炎症、氧化应激和线粒体功能障碍导致神经元变性。在这里,我们试图阐明细胞外Hb和血红素的促氧化和炎症作用,强调它们对AD和PD发展的潜在影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
6.60
自引率
8.10%
发文量
72
审稿时长
6-12 weeks
期刊介绍: Biomolecules & Therapeutics (Biomolecules & Therapeutics) (Print ISSN 1976-9148, Online ISSN 2005-4483) is an international, peer-reviewed, open access journal that covers pharmacological and toxicological fields related to bioactive molecules and therapeutics. It was launched in 1993 as "The Journal of Applied Pharmacology (ISSN 1225-6110)", and renamed "Biomolecules & Therapeutics" (Biomol Ther: abbreviated form) in 2008 (Volume 16, No. 1). It is published bimonthly in January, March, May, July, September and November. All manuscripts should be creative, informative, and contribute to the development of new drugs. Articles in the following categories are published: review articles and research articles.
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