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Physiological and Pathological Functions of Neuronal Hemoglobin: A Key Underappreciated Protein in Parkinson’s Disease

The expression of Hemoglobin (Hb) is not restricted to erythrocytes but is also present in neurons. Hb is selectively enriched in vulnerable mesencephalic dopaminergic neurons of Parkinson’s disease (PD) instead of resistant neurons. Controversial results of neuronal Hb levels have been reported in...

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Autores principales: Zheng, Ran, Yan, Yiqun, Pu, Jiali, Zhang, Baorong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9408843/
https://www.ncbi.nlm.nih.gov/pubmed/36012351
http://dx.doi.org/10.3390/ijms23169088
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author Zheng, Ran
Yan, Yiqun
Pu, Jiali
Zhang, Baorong
author_facet Zheng, Ran
Yan, Yiqun
Pu, Jiali
Zhang, Baorong
author_sort Zheng, Ran
collection PubMed
description The expression of Hemoglobin (Hb) is not restricted to erythrocytes but is also present in neurons. Hb is selectively enriched in vulnerable mesencephalic dopaminergic neurons of Parkinson’s disease (PD) instead of resistant neurons. Controversial results of neuronal Hb levels have been reported in postmortem brains of PD patients: although neuronal Hb levels may decline in PD patients, elderly men with higher Hb levels have an increased risk of developing PD. α-synuclein, a key protein involved in PD pathology, interacts directly with Hb protein and forms complexes in erythrocytes and brains of monkeys and humans. These complexes increase in erythrocytes and striatal cytoplasm, while they decrease in striatal mitochondria with aging. Besides, the colocalization of serine 129-phosphorylated (Pser129) α-synuclein and Hb β chains have been found in the brains of PD patients. Several underlying molecular mechanisms involving mitochondrial homeostasis, α-synuclein accumulation, iron metabolism, and hormone-regulated signaling pathways have been investigated to assess the relationship between neuronal Hb and PD development. The formation of fibrils with neuronal Hb in various neurodegenerative diseases may indicate a common fibrillization pathway and a widespread target that could be applied in neurodegeneration therapy.
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spelling pubmed-94088432022-08-26 Physiological and Pathological Functions of Neuronal Hemoglobin: A Key Underappreciated Protein in Parkinson’s Disease Zheng, Ran Yan, Yiqun Pu, Jiali Zhang, Baorong Int J Mol Sci Review The expression of Hemoglobin (Hb) is not restricted to erythrocytes but is also present in neurons. Hb is selectively enriched in vulnerable mesencephalic dopaminergic neurons of Parkinson’s disease (PD) instead of resistant neurons. Controversial results of neuronal Hb levels have been reported in postmortem brains of PD patients: although neuronal Hb levels may decline in PD patients, elderly men with higher Hb levels have an increased risk of developing PD. α-synuclein, a key protein involved in PD pathology, interacts directly with Hb protein and forms complexes in erythrocytes and brains of monkeys and humans. These complexes increase in erythrocytes and striatal cytoplasm, while they decrease in striatal mitochondria with aging. Besides, the colocalization of serine 129-phosphorylated (Pser129) α-synuclein and Hb β chains have been found in the brains of PD patients. Several underlying molecular mechanisms involving mitochondrial homeostasis, α-synuclein accumulation, iron metabolism, and hormone-regulated signaling pathways have been investigated to assess the relationship between neuronal Hb and PD development. The formation of fibrils with neuronal Hb in various neurodegenerative diseases may indicate a common fibrillization pathway and a widespread target that could be applied in neurodegeneration therapy. MDPI 2022-08-13 /pmc/articles/PMC9408843/ /pubmed/36012351 http://dx.doi.org/10.3390/ijms23169088 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Zheng, Ran
Yan, Yiqun
Pu, Jiali
Zhang, Baorong
Physiological and Pathological Functions of Neuronal Hemoglobin: A Key Underappreciated Protein in Parkinson’s Disease
title Physiological and Pathological Functions of Neuronal Hemoglobin: A Key Underappreciated Protein in Parkinson’s Disease
title_full Physiological and Pathological Functions of Neuronal Hemoglobin: A Key Underappreciated Protein in Parkinson’s Disease
title_fullStr Physiological and Pathological Functions of Neuronal Hemoglobin: A Key Underappreciated Protein in Parkinson’s Disease
title_full_unstemmed Physiological and Pathological Functions of Neuronal Hemoglobin: A Key Underappreciated Protein in Parkinson’s Disease
title_short Physiological and Pathological Functions of Neuronal Hemoglobin: A Key Underappreciated Protein in Parkinson’s Disease
title_sort physiological and pathological functions of neuronal hemoglobin: a key underappreciated protein in parkinson’s disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9408843/
https://www.ncbi.nlm.nih.gov/pubmed/36012351
http://dx.doi.org/10.3390/ijms23169088
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