Your search for: 'author:("Mancuso, Cesare")' has returned 3 results. (0.01s) Save search

Authors: Barone, Eugenio | Di Domenico, Fabio | Cenini, Giovanna | Sultana, Rukhsana | Coccia, Raffaella | Preziosi, Paolo | Perluigi, Marzia | Mancuso, Cesare | Butterfield, D. Allan

Article Type: Research Article

Abstract: Biliverdin reductase-A (BVR-A) is a pleiotropic enzyme and plays pivotal role in the antioxidant defense against free radicals as well as in cell homeostasis. Together with heme oxygenase, BVR-A forms a powerful system involved in the cell stress response during neurodegenerative disorders including Alzheimer's disease (AD), whereas due to the serine/threonine/tyrosine kinase activity the enzyme regulates glucose metabolism and cell proliferation. In this paper, we report results that demonstrate BVR-A undergoes post-translational oxidative and nitrosative modifications in the hippocampus, but not cerebellum, of subjects with AD and amnestic mild cognitive impairment (MCI). A significant increase of nitrated BVR-A was demonstrated …only in AD and MCI hippocampi, whereas no significant modifications were found in cerebellar tissue. In addition, a significant reduction in protein carbonyl-derivatives of BVR-A was found in both AD and MCI hippocampi (15% and 18%, respectively). Biliverdin reductase-bound 4-hydroxynonenals were not modified in hippocampi and cerebella from AD and MCI subjects. These results supported the hypothesis of a prevalence of nitrosative stress-induced modifications on BVR-A structure, and this evidence was confirmed by a significant upregulation of inducible nitric oxide synthase in hippocampal tissue of subjects with AD and MCI that was not present in cerebellum. In conclusion, nitrosative stress-induced modifications on hippocampal BVR-A are an early event in the pathogenesis of AD since they appear also in MCI subjects and could contribute to the antioxidant and metabolic derangement characteristic of these neurodegenerative disorders. Show more

Keywords: Alzheimer's disease, biliverdin reductase, heme oxygenase, mild cognitive impairment, neurodegenerative disorders, oxidative stress

DOI: 10.3233/JAD-2011-110092

Citation: Journal of Alzheimer's Disease, vol. 25, no. 4, pp. 623-633, 2011

Authors: Di Domenico, Fabio | Barone, Eugenio | Mancuso, Cesare | Perluigi, Marzia | Cocciolo, Annalisa | Mecocci, Patrizia | Butterfield, D. Allan | Coccia, Raffaella

Article Type: Research Article

Abstract: Several studies showed increased oxidative and nitrosative stress in plasma from patients with Alzheimer's disease (AD), however, little and controversial knowledge has emerged about the antioxidant functionality of the heme oxygenase-1/biliverdin reductase-A (HO-1/BVR-A) system in blood. The current study reports increased levels of both HO-1 and BVR-A in plasma from probable AD patients, as a result of the increased oxidative environment. However, the increase of oxidative stress in plasma result also in the increase of BVR-A 3-nitrotyrosine levels and the decrease of BVR-A phosphotyrosine levels and reductase activity, suggesting that nitrosative stress play the prominent oxidative role in plasma during …AD. Our data on HO-1/BVR-A status in plasma closely correlate with recent reports in hippocampus of subjects with AD and arguably its early form, mild cognitive impairment. Moreover, we show that alterations on HO-1/BVR-A system are tightly connected with cognitive decline indexed by Mini-Mental Status Exam scores. We hypothesize that the HO-1/BVR-A system status in plasma might reflect the ongoing situation in the brain, offering an important biochemical tool for the potential prediction of AD at the earliest stages of the disease. Show more

Keywords: Alzheimer disease's, bilirubin, biliverdin reductase-A, heme oxygenase-1, oxidative/nitrosative stress

DOI: 10.3233/JAD-2012-121045

Citation: Journal of Alzheimer's Disease, vol. 32, no. 2, pp. 277-289, 2012

Authors: Di Domenico, Fabio | Pupo, Gilda | Mancuso, Cesare | Barone, Eugenio | Paolini, Francesca | Arena, Andrea | Blarzino, Carla | Schmitt, Frederick A. | Head, Elizabeth | Butterfield, D. Allan | Perluigi, Marzia

Article Type: Research Article

Abstract: Bach1, among the genes encoded on chromosome 21, is a transcription repressor, which binds to antioxidant response elements of DNA thus inhibiting the transcription of specific genes involved in the cell stress response including heme oxygenase-1 (HO-1). HO-1 and its partner, biliverdin reductase-A (BVR-A), are upregulated in response to oxidative stress in order to protect cells against further damage. Since oxidative stress is an early event in Down syndrome (DS) and might contribute to the development of multiple deleterious DS phenotypes, including Alzheimer's disease (AD) pathology, we investigated the status of the Bach1/HO-1/BVR-A axis in DS and its possible implications …for the development of AD. In the present study, we showed increased total Bach1 protein levels in the brain of all DS cases coupled with reduced induction of brain HO-1. Furthermore, increased oxidative stress could, on one hand, overcome the inhibitory effects of Bach1 and, on the other hand, promote BVR-A impairment. Our data show that the development of AD in DS subjects is characterized by (i) increased Bach1 total and poly-ubiquitination; (ii) increased HO-1 protein levels; and (iii) increased nitration of BVR-A followed by reduced activity. To corroborate our findings, we analyzed Bach1, HO-1, and BVR-A status in the Ts65Dn mouse model at 3 (young) and 15 (old) months of age. The above data support the hypothesis that the dysregulation of HO-1/BVR-A system contributes to the early increase of oxidative stress in DS and provide potential mechanistic paths involved in the neurodegenerative process and AD development. Show more

Keywords: Bach1, biliverdin reductase, heme oxygenase, oxidative stress, trisomy 21

DOI: 10.3233/JAD-141254

Citation: Journal of Alzheimer's Disease, vol. 44, no. 4, pp. 1107-1120, 2015