Search

Your search keyword '"bilivedin reductase-A"' showing total 2 results
Start Over Descriptor "bilivedin reductase-A" Topic amyloid precursor protein secretases
2 results on '"bilivedin reductase-A"'

1. Biliverdin reductase-A impairment links brain insulin resistance with increased Aβ production in an animal model of aging: Implications for Alzheimer disease.

Author

Triani F, Tramutola A, Di Domenico F, Sharma N, Butterfield DA, Head E, Perluigi M, and Barone E

Subjects
Aged, Animals, Cyclin-Dependent Kinase Inhibitor Proteins metabolism, Disease Models, Animal, Dogs, HEK293 Cells, Humans, Insulin Resistance, Male, Phosphorylation, Aging metabolism, Alzheimer Disease metabolism, Amyloid Precursor Protein Secretases metabolism, Amyloid beta-Protein Precursor metabolism, Aspartic Acid Endopeptidases metabolism, Brain metabolism, Oxidoreductases Acting on CH-CH Group Donors metabolism
Abstract

Brain insulin resistance is associated with an increased Aβ production in AD although the molecular mechanisms underlying this link are still largely unknown. Biliverdin reductase-A (BVR-A) is a unique Ser/Thr/Tyr kinase regulating insulin signalling. Studies from our group, demonstrated that BVR-A impairment is among the earliest events favoring brain insulin resistance development. Furthermore, reported a negative association between BVR-A protein levels/activation and BACE1 protein levels in the parietal cortex of aged beagles (an animal model of AD), thus suggesting a possible interaction. Therefore, we aimed to demonstrate that BVR-A impairment is a molecular bridge linking brain insulin resistance with increased Aβ production. Age-associated changes of BVR-A, BACE1, insulin signalling cascade and APP processing were evaluated in the parietal cortex of beagles and experiments to confirm the hypothesized mechanism(s) have been performed in vitro in HEK293APPswe cells. Our results show that BVR-A impairment occurs early with age and is associated with brain insulin resistance. Furthermore, we demonstrate that BVR-A impairment favors CK1-mediated Ser phosphorylation of BACE1 (known to mediate BACE1 recycling to plasma membrane) along with increased Aβ production in the parietal cortex, with age. Overall, our results suggest that the impairment of BVR-A is an early molecular event contributing to both (I) the onset of brain insulin resistance and (II) the increased Aβ production observed in AD. We, therefore, suggest that by targeting BVR-A activity it could be possible to delay the onset of brain insulin resistance along with an improved regulation of the APP processing., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Published
2018
Full Text
View/download PDF

2. Biliverdin reductase-A impairment links brain insulin resistance with increased Aβ production in an animal model of aging: implications for Alzheimer disease

Author

Eugenio Barone, Nidhi Sharma, Francesca Triani, Marzia Perluigi, Elizabeth Head, D. Allan Butterfield, Fabio Di Domenico, and Antonella Tramutola

Subjects
Male, 0301 basic medicine, Aging, Oxidoreductases Acting on CH-CH Group Donors, medicine.medical_specialty, bace1, Posterior parietal cortex, canine, Amyloid beta-Protein Precursor, 03 medical and health sciences, chemistry.chemical_compound, Dogs, 0302 clinical medicine, Insulin resistance, Internal medicine, insulin resistance, medicine, Animals, Aspartic Acid Endopeptidases, Humans, molecular biology, Phosphorylation, Aged, Cyclin-Dependent Kinase Inhibitor Proteins, molecular medicine, Biliverdin, business.industry, Kinase, Biliverdin reductase, Brain, medicine.disease, In vitro, bilivedin reductase-A, Disease Models, Animal, HEK293 Cells, 030104 developmental biology, Endocrinology, chemistry, dog, Amyloid Precursor Protein Secretases, Alzheimer's disease, Alzheimer disease, business, 030217 neurology & neurosurgery
Abstract

Brain insulin resistance is associated with an increased Aβ production in AD although the molecular mechanisms underlying this link are still largely unknown. Biliverdin reductase-A (BVR-A) is a unique Ser/Thr/Tyr kinase regulating insulin signalling. Studies from our group, demonstrated that BVR-A impairment is among the earliest events favoring brain insulin resistance development. Furthermore, reported a negative association between BVR-A protein levels/activation and BACE1 protein levels in the parietal cortex of aged beagles (an animal model of AD), thus suggesting a possible interaction. Therefore, we aimed to demonstrate that BVR-A impairment is a molecular bridge linking brain insulin resistance with increased Aβ production. Age-associated changes of BVR-A, BACE1, insulin signalling cascade and APP processing were evaluated in the parietal cortex of beagles and experiments to confirm the hypothesized mechanism(s) have been performed in vitro in HEK293APPswe cells. Our results show that BVR-A impairment occurs early with age and is associated with brain insulin resistance. Furthermore, we demonstrate that BVR-A impairment favors CK1-mediated Ser phosphorylation of BACE1 (known to mediate BACE1 recycling to plasma membrane) along with increased Aβ production in the parietal cortex, with age. Overall, our results suggest that the impairment of BVR-A is an early molecular event contributing to both (I) the onset of brain insulin resistance and (II) the increased Aβ production observed in AD. We, therefore, suggest that by targeting BVR-A activity it could be possible to delay the onset of brain insulin resistance along with an improved regulation of the APP processing.

Published
2018

Catalog

Books, media, physical & digital resources
See catalog results