Inflaming the Brain with Iron
| Autor: | Daniel A. Bórquez, Pamela J. Urrutia, Marco T. Núñez |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Physiology Clinical Biochemistry Inflammation Review Mitochondrion medicine.disease_cause Biochemistry Aconitase Nitric oxide neuroinflammation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine iron Hepcidin nitric oxide medicine oxidative stress Molecular Biology Neuroinflammation biology Microglia lcsh:RM1-950 iron regulatory protein 1 Cell Biology Cell biology lcsh:Therapeutics. Pharmacology 030104 developmental biology medicine.anatomical_structure chemistry biology.protein Parkinson’s disease hepcidin medicine.symptom Alzheimer’s disease 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Antioxidants Antioxidants, Vol 10, Iss 61, p 61 (2021) |
| ISSN: | 2076-3921 |
| Popis: | Iron accumulation and neuroinflammation are pathological conditions found in several neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Iron and inflammation are intertwined in a bidirectional relationship, where iron modifies the inflammatory phenotype of microglia and infiltrating macrophages, and in turn, these cells secrete diffusible mediators that reshape neuronal iron homeostasis and regulate iron entry into the brain. Secreted inflammatory mediators include cytokines and reactive oxygen/nitrogen species (ROS/RNS), notably hepcidin and nitric oxide (·NO). Hepcidin is a small cationic peptide with a central role in regulating systemic iron homeostasis. Also present in the cerebrospinal fluid (CSF), hepcidin can reduce iron export from neurons and decreases iron entry through the blood–brain barrier (BBB) by binding to the iron exporter ferroportin 1 (Fpn1). Likewise, ·NO selectively converts cytosolic aconitase (c-aconitase) into the iron regulatory protein 1 (IRP1), which regulates cellular iron homeostasis through its binding to iron response elements (IRE) located in the mRNAs of iron-related proteins. Nitric oxide-activated IRP1 can impair cellular iron homeostasis during neuroinflammation, triggering iron accumulation, especially in the mitochondria, leading to neuronal death. In this review, we will summarize findings that connect neuroinflammation and iron accumulation, which support their causal association in the neurodegenerative processes observed in AD and PD. |
| Databáze: | OpenAIRE |
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