scholarly journals Relationship between Brain Tissue Changes and Blood Biomarkers of Cyclophilin A, Heme Oxygenase-1, and Inositol-Requiring Enzyme 1 in Patients with Alzheimer’s Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 740
Author(s):  
Hyon-Il Choi ◽  
Kiyoon Kim ◽  
Jiyoon Lee ◽  
Yunjung Chang ◽  
Hak Young Rhee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Globus Pallidus ◽  
Serum Protein ◽  
Heme Oxygenase ◽  
Brain Magnetic Resonance Imaging ◽  
Cyclophilin A ◽  
Blood Levels ◽  
Heme Oxygenase 1 ◽  
Protein Levels

Cyclophilin A (CypA), heme oxygenase-1 (HO-1), and inositol-requiring enzyme 1 (IRE1) are believed to be associated with Alzheimer’s disease (AD). In this study, we investigated the association between gray matter volume (GMV) changes and blood levels of CypA, HO-1, and IRE1 in cognitively normal (CN) subjects and those with amnestic mild cognitive impairment (aMCI) and AD. Forty-five elderly CN, 34 aMCI, and 39 AD subjects were enrolled in this study. The results of voxel-based multiple regression analysis showed that blood levels of CypA, HO-1, and IRE1 were correlated with GMV on brain magnetic resonance imaging (MRI) in the entire population (p = 0.0005). The three serum protein levels were correlated with GMV of signature AD regions in the population as a whole. CypA values increased with increasing GMV in the occipital gyrus (r = 0.387, p < 0.0001) and posterior cingulate (r = 0.196, p = 0.034). HO-1 values increased with increasing GMV at the uncus (r = 0.307, p = 0.0008), lateral globus pallidus and putamen (r = 0.287, p = 0.002), and hippocampus (r = 0.197, p = 0.034). IRE1 values decreased with increasing GMV at the uncus (r = −0.239, p = 0.010) and lateral globus pallidus and putamen (r = −0.335, p = 0.0002). Associations between the three serum protein levels and regional GMV indicate that the blood levels of these biomarkers may reflect the pathological mechanism of AD in the brain.

Induction of Heme Oxygenase-1 mRNA and Protein in Neocortex and Cerebral Vessels in Alzheimer's Disease

2002 ◽  
Vol 65 (3) ◽  
pp. 1399-1402 ◽  
Author(s):  
Daniel R. D. Premkumar ◽  
Mark A. Smith ◽  
Peggy L. Richey ◽  
Robert B. Petersen ◽  
Rudy Castellani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heme Oxygenase ◽  
Cerebral Vessels ◽  
Heme Oxygenase 1

Regulation of Heme Oxygenase Expression by Cyclopentenone Prostaglandins

2003 ◽  
Vol 228 (5) ◽  
pp. 499-505 ◽  
Author(s):  
Hean Zhuang ◽  
Sokhon Pin ◽  
Xiaoling Li ◽  
Sylvain Doré
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heme Oxygenase ◽  
Significant Role ◽  
Neuronal Cell ◽  
Heme Oxygenase 1 ◽  
Neuronal Cultures ◽  
Dependent Manner ◽  
Stress Injury ◽  
Free Radical Damage

Prostaglandins (PGs) originate from the degradation of membranar arachidonic acid by cyclooxygenases (COX-1 and COX-2). The prostaglandin actions in the nervous system are multiple and have been suggested to play a significant role in neurodegenerative disorders. Some PGs have been reported to be toxic and, interestingly, the cyclopentenone PGs have been reported to be cytoprotective at low concentration and could play a significant role in neuronal plasticity. They have been shown to be protective against oxidative stress injury; however, the cellular mechanisms of protection afforded by these PGs are still unclear. It is postulated that the cascade leading to neuronal cell death in acute and chronic neurodegenerative conditions, such as cerebral ischemia and Alzheimer’s disease, would be mediated by free radical damage. We tested the hypothesis that the neuroprotective action of cyclopentanone could be caused partially by an induction of heme oxygenase 1 (HO-1). We and others have previously reported that modulation of HO total activity may well have direct physiological implications in stroke and in Alzheimer’s disease. HO acts as an antioxidant enzyme by degrading heme into iron, carbon monoxide, and biliverdin that is rapidly converted into bilirubin. Using mouse primary neuronal cultures, we demonstrated that PGs of the J series induce HO-1 in a dose-dependent manner (0, 0.5, 5, 10, 20, and 50 μg/ml) and that PGJ2 and dPGJ2 were more potent than PGA2, dPGA2, PGD2, and PGE2. No significant effects were observed for HO-2 and actin expression. In regard to HO-3 expression found in rat, with its protein deducted sequence highly homologous to HO-2, no detection was observed in HO-2−/− mice, suggesting that HO-3 protein would not be present in mouse brain. We are proposing that several of the protective effects of PGJ2 could be mediated through beneficial actions of heme degradation and its metabolites. The design of new mimetics based on the cyclopentenone structure could be very useful as neuroprotective agents and be tested in animal models of stroke and Alzheimer’s disease.

Gene–gene interaction between heme oxygenase-1 and liver X receptor-β and Alzheimer's disease risk

2010 ◽  
Vol 31 (4) ◽  
pp. 710-714 ◽  
Author(s):  
Jon Infante ◽  
Eloy Rodríguez-Rodríguez ◽  
Ignacio Mateo ◽  
Javier Llorca ◽  
José Luis Vázquez-Higuera ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heme Oxygenase ◽  
Disease Risk ◽  
Gene Interaction ◽  
Liver X Receptor ◽  
Heme Oxygenase 1

scholarly journals Amyloid Beta-Mediated Hypomethylation of Heme Oxygenase 1 Correlates with Cognitive Impairment in Alzheimer’s Disease

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153156 ◽  
Author(s):  
Hye Youn Sung ◽  
Byung-Ok Choi ◽  
Jee Hyang Jeong ◽  
Kyoung Ae Kong ◽  
Jinha Hwang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Heme Oxygenase ◽  
Amyloid Beta ◽  
Heme Oxygenase 1

scholarly journals Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 644 ◽  
Author(s):  
Cristina Fernández-Mendívil ◽  
Miguel A. Arreola ◽  
Lindsay A. Hohsfield ◽  
Kim N. Green ◽  
Manuela G. Lopez
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heme Oxygenase ◽  
Beta Amyloid ◽  
Postmortem Brain ◽  
Heme Oxygenase 1 ◽  
Total Brain ◽  
Potential Biomarker ◽  
Brain Expression ◽  
5Xfad Mice

Neuroinflammation and oxidative stress are being recognized as characteristic hallmarks in many neurodegenerative diseases, especially those that portray proteinopathy, such as Alzheimer’s disease (AD). Heme-oxygenase 1 (HO-1) is an inducible enzyme with antioxidant and anti-inflammatory properties, while microglia are the immune cells in the central nervous system. To elucidate the brain expression profile of microglial HO-1 in aging and AD-progression, we have used the 5xFAD (five familial AD mutations) mouse model of AD and their littermates at different ages (four, eight, 12, and 18 months). Total brain expression of HO-1 was increased with aging and such increase was even higher in 5xFAD animals. In co-localization studies, HO-1 expression was mainly found in microglia vs. other brain cells. The percentage of microglial cells expressing HO-1 and the amount of HO-1 expressed within microglia increased progressively with aging. Furthermore, this upregulation was increased by 2–3-fold in the elder 5xFAD mice. In addition, microglia overexpressing HO-1 was predominately found surrounding beta-amyloid plaques. These results were corroborated using postmortem brain samples from AD patients, where microglial HO-1 was found up-regulated in comparison to brain samples from aged matched non-demented patients. This study demonstrates that microglial HO-1 expression increases with aging and especially with AD progression, highlighting HO-1 as a potential biomarker or therapeutic target for AD.

The Neuroprotective and Neurodegeneration Effects of Heme Oxygenase-1 in Alzheimer’s Disease

2020 ◽  
Vol 78 (4) ◽  
pp. 1259-1272
Author(s):  
Zizhen Si ◽  
Xidi Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Heme Oxygenase 1 ◽  
Molecular Processes ◽  
Disease Modifying Therapies

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by complex pathological and biological features. Notably, extracellular amyloid-β deposits as senile plaques and intracellular aggregation of hyperphosphorylated tau as neurofibrillary tangles remain the primary premortem criterion for the diagnosis of AD. Currently, there exist no disease-modifying therapies for AD, and many clinical trials have failed to show its benefits for patients. Heme oxygenase 1 (HO-1) is a 32 kDa enzyme, which catalyzes the degradation of cellular heme to free ferrous iron, biliverdin, and carbon monoxide under stressful conditions. Several studies highlight the crucial pathological roles of HO-1 in the molecular processes of AD. The beneficial roles of HO-1 overexpression in AD brains are widely accepted due to its ability to convert pro-oxidant heme to biliverdin and bilirubin (antioxidants), which promote restoration of a suitable tissue redox microenvironment. However, the intracellular oxidative stress might be amplified by metabolites of HO-1 and exacerbate the progression of AD under certain circumstances. Several lines of evidence have demonstrated that upregulated HO-1 is linked to tauopathies, neuronal damage, and synapse aberrations in AD. Here, we review the aspects of the molecular mechanisms by which HO-1 regulates AD and the latest information on the pathobiology of AD. We further highlight the neuroprotective and neurodystrophic actions of HO-1 and the feasibility of HO-1 as a therapeutic target for AD.

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