{"title":"Pro-Oxidative and Inflammatory Actions of Extracellular Hemoglobin and Heme: Molecular Events and Implications for Alzheimer's and Parkinson Disease.","authors":"Nicole Bon Campomayor, Hee Jin Kim, Mikyung Kim","doi":"10.4062/biomolther.2024.224","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"235-248"},"PeriodicalIF":3.0000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893490/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomolecules & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4062/biomolther.2024.224","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/18 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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.