Hemoglobin promotes A? oligomer formation and localizes in neurons and amyloid deposits

Wu, Chun Ying; Liao, Pao Chi; Yu, Lung; Wang, Shan Tair; Chen, Shur Tzu; Wu, Ching Ming; Kuo, Yu Min

doi:10.1016/j.nbd.2004.08.014

Cited by 91 publications

(94 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rogers et al, 1992;Ma et al, 1994;Schwarzman et al, 1994;Snow et al, 1994;Eriksson et al, 1995;Zlokovic et al, 1996;Wu et al, 2004). Of the various binding mechanisms, one that has attracted particular attention is the effect of metal ions on A␤ precipitation and toxicity (Bush et al, 1993(Bush et al, , 1994Rottkamp et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Kinetic analysis of β-amyloid peptide aggregation induced by metal ions based on surface plasmon resonance biosensing

Chang

Chen

et al. 2006

Journal of Neuroscience Methods

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Kinetic analysis of β-amyloid peptide aggregation induced by metal ions based on surface plasmon resonance biosensing

Chang

Chen

et al. 2006

Journal of Neuroscience Methods

View full text Add to dashboard Cite

Section: Hb and Heme In Ad Brains And Its Vasculaturementioning

confidence: 99%

“…While isolating specific proteins with strong affinity for Aβ, one group of investigators reported the α chain of hemoglobin (Hb) as one of only a few proteins recovered and identified from rat brain homogenates [72]. In addition, Hb has been co-immunoprecipitated with Aβ from both AD brains and plasma [53,72,105]. …”

Section: Aβ Binding With Hbmentioning

confidence: 99%

“…Hb, Hb derived peptides, and Hb mRNA levels have been reported to be increased in AD brains relative to the brains of non-demented control subjects [17,75,85,91,105]. Brain Hb levels in AD were highest in the hippocampus and parietal gray and white matter and lowest in the cerebellum, and there was co-localization of Hb with senile plaques and CAA [105]. The increased presence of Hb and its breakdown products in the brain is probably derived from erythrocytes in the circulation as a result of injury to the endothelium and the BBB with subsequent leakage of plasma or blood components into the perivascular space where additional heme iron-mediated damage may occur [17].…”

Section: Hb and Heme In Ad Brains And Its Vasculaturementioning

confidence: 99%

See 1 more Smart Citation

Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease

Perry

Gearhart

Wiener

et al. 2008

Neurobiology of Aging

View full text Add to dashboard Cite

From a normal human brain phage display library screen we identified the gamma (A)-globin chain of fetal hemoglobin (Hb F) as a protein that bound strongly to Aβ1-42. We showed the oxidized form 1 These authors are co-corresponding authors for all stages of refereeing and publication and contributed equally to this work. Rodney T. Perry; Rm. 210H, 1665 University Blvd.; University of Alabama at Birmingham, Birmingham, USA; Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosure Statement:I so state for myself and on behalf of the other authors on the manuscript, Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease, that we have no conflicts and sources of funding that influence the results of this paper, the data is not published or submitted elsewhere, and that appropriate approval and procedures were used concerning human subjects. I also verify that all authors on this manuscript have reviewed the contents of the manuscript, approve of its contents, and validate the accuracy of the data. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript of adult Hb (metHb A) binds with greater affinity to Aβ1-42 than metHb F. MetHb is more toxic than oxyhemoglobin because it loses its heme group more readily. Free Hb and heme readily damage vascular endothelial cells similar to Alzheimer's disease (AD) vascular pathology. The XmnI polymorphism (C→T) at −158 of the gamma (G)-globin promoter region can contribute to increased Hb F expression. Using family-based association testing, we found a significant protective association of this polymorphism in the NIMH sibling dataset (n=489) in families, with at least two affected and one unaffected sibling (p=0.006), with an age of onset >50 years (p=0.010) and >65 years (p=0.013), and families not homozygous for the APOE4 allele (p=0.041). We hypothesize that Hb F may be less toxic than adult Hb in its interaction with Aβ and may protect against the development of AD.

show abstract

“…Indeed, there is a close relationship between the amount of hemoglobin in the brain and Parkinson's disease (Shephard et al, 2014). In Alzheimer's disease, hemoglobin bound to amyloid-β (Aβ) facilitating Aβ aggregation has been detected especially in hippocampus of patients and is upregulated according to age (Wu et al, 2004;Chuang et al, 2012). Hemoglobin induces ROS and DNA damage in vitro, and HbA upregulation is associated with colitis-related colorectal cancer (Myers et al, 2014).…”

Section: Hba Proteinmentioning

confidence: 99%

Maternal administration of nanomaterials elicits hemoglobin upregulation in the neonatal brain of non-human primates

et al. 2016

View full text Add to dashboard Cite

-To investigate the influence of nanomaterial exposure during fetal development, diesel exhaust particles (DEPs), carbon black (CB), or titanium dioxide (TiO 2 ) was injected intradermally to pregnant rhesus macaques. The hippocampus and cerebellum of newborn infants were then examined. DNA microarray and quantitative real-time RT-PCR, western blot, and immunohistochemical analyses were used to measure the expression of the hemoglobin genes, HBA, HBB, and HBG. Of the nanomaterials tested, DEP elicited the greatest increase in mRNA and protein levels of hemoglobin genes in the brain tissues. Strong signal of HbA protein was detected in the pyramidal cell layer, the polymorphic cell layer and in the alveus of the hippocampi of the DEP-treated animals. The altered gene expression was likely due to responses to oxidative or nitrosative stress and/or hypoxia in the fetal/neonatal brain. Since excessive hemoglobin is reportedly neurotoxic, the vulnerability of developing brains by long-term upregulation of hemoglobin should be considered. Maternal exposure to nanomaterials may increase the risk of brain dysfunction in offspring.

show abstract

Hemoglobin promotes A? oligomer formation and localizes in neurons and amyloid deposits

Cited by 91 publications

References 44 publications

Kinetic analysis of β-amyloid peptide aggregation induced by metal ions based on surface plasmon resonance biosensing

Kinetic analysis of β-amyloid peptide aggregation induced by metal ions based on surface plasmon resonance biosensing

Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease

Maternal administration of nanomaterials elicits hemoglobin upregulation in the neonatal brain of non-human primates

Contact Info

Product

Resources

About