The mesencephalic dopaminergic (mDA) cell system is composed of two major groups of projecting cells in the substantia nigra (SN) (A9 neurons) and the ventral tegmental area (VTA) (A10 cells). A9 neurons form the nigrostriatal pathway and are involved in regulating voluntary movements and postural reflexes. Their selective degeneration leads to Parkinson's disease. Here, we report that gene expression analysis of A9 dopaminergic neurons (DA) identifies transcripts for alpha- and beta-chains of hemoglobin (Hb). Globin immunoreactivity decorates the majority of A9 DA, a subpopulation of cortical and hippocampal astrocytes and mature oligodendrocytes. This pattern of expression was confirmed in different mouse strains and in rat and human. We show that Hb is expressed in the SN of human postmortem brain. By microarray analysis of dopaminergic cell lines overexpressing alpha- and beta-globin chains, changes in genes involved in O(2) homeostasis and oxidative phopshorylation were observed, linking Hb expression to mitochondrial function. Our data suggest that the most famed oxygen-carrying globin is not exclusively restricted to the blood, but it may play a role in the normal physiology of the brain and neurodegenerative diseases.
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http://dx.doi.org/10.1073/pnas.0813216106 | DOI Listing |
Cell Rep
January 2025
Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli & Edythe Broad Center for Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Bioengineering & Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address:
The most severe form of α-thalassemia results from loss of all four copies of α-globin. Postnatally, patients face challenges similar to β-thalassemia, including severe anemia and erythrotoxicity due to the imbalance of β-globin and α-globin chains. Despite progress in genome editing treatments for β-thalassemia, there is no analogous curative option for α-thalassemia.
View Article and Find Full Text PDFFront Mol Biosci
December 2024
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United States.
Introduction: Sickle cell disease (SCD) is a genetic blood disorder caused by a mutation in the HBB gene, which encodes the beta-globin subunit of hemoglobin. This mutation leads to the production of abnormal hemoglobin S (HbS), causing red blood cells to deform into a sickle shape. These deformed cells can block blood flow, leading to complications like chronic hemolysis, anemia, severe pain episodes, and organ damage.
View Article and Find Full Text PDFCureus
November 2024
Community Medicine, Baba Raghav Das Medical College, Gorakhpur, IND.
Ann Hematol
December 2024
Rare Disease Medical Center, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian Province, China.
Introduction: β-thalassemia is a common genetic disease mainly caused by point mutations in the β-globin gene, eliciting a high prevalence in South China. The aim of the present study is to identify a rare HBB: c.316-90 A > G variant and provide the clinical and hematological features in two unrelated Chinese families.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Innovation Center for Diagnostics and Treatment of Thalassemia, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Despite the well-documented mutation spectra of β-thalassemia, the genetic variants and haplotypes of globin gene clusters modulating its clinical heterogeneity remain incompletely illustrated. Here, a targeted long-read sequencing (T-LRS) is demonstrated to capture 20 genes/loci in 1,020 β-thalassemia patients. This panel permits not only identification of thalassemia mutations at 100% of sensitivity and specificity, but also detection of rare structural variants (SVs) and single nucleotide variants (SNVs) in modifier genes/loci.
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