Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Pharmacological intervention in a transgenic mouse model improves Alzheimer's-associated pathological phenotype: Involvement of proteasome activation
Δημιουργός/Συγγραφέας:	Mladenovic Djordjevic, Aleksandra N Kapetanou, Marianna Loncarevic-Vasiljkovic, Natasa Todorovic, Smilja Athanasopoulou, Sofia Jovic, Milena Prvulovic, Milica Taoufik, Era Matsas, Rebecca Kanazir, Selma [EL] Γκόνος, Ευστάθιος[EN] Gonos, Efstathios S.
Εκδότης:	Elsevier
Ημερομηνία:	2021-01
Γλώσσα:	Αγγλικά
ISSN:	08915849
DOI:	10.1016/j.freeradbiomed.2020.11.038
Άλλο:	33279620
Περίληψη:	Alzheimer's disease (AD) is the most common form of dementia worldwide, characterized by a progressive decline in a variety of cognitive and non-cognitive functions. The amyloid beta protein cascade hypothesis places the formation of amyloid beta protein aggregates on the first position in the complex pathological cascade leading to neurodegeneration, and therefore AD might be considered to be a protein-misfolding disease. The Ubiquitin Proteasome System (UPS), being the primary protein degradation mechanism with a fundamental role in the maintenance of proteostasis, has been identified as a putative therapeutic target to delay and/or to decelerate the progression of neurodegenerative disorders that are characterized by accumulated/aggregated proteins. The purpose of this study was to test if the activation of proteasome in vivo can alleviate AD pathology. Specifically by using two compounds with complementary modes of proteasome activation and documented antioxidant and redox regulating properties in the 5xFAD transgenic mice model of AD, we ameliorated a number of AD related deficits. Shortly after proteasome activation we detected significantly reduced amyloid-beta load correlated with improved motor functions, reduced anxiety and frailty level. Essentially, to our knowledge this is the first report to demonstrate a dual activation of the proteasome and its downstream effects. In conclusion, these findings open up new directions for future therapeutic potential of proteasome-mediated proteolysis enhancement.
Τίτλος πηγής δημοσίευσης:	Free radical biology & medicine
Τόμος/Κεφάλαιο:	162
Σελίδες:	88-103
Θεματική Κατηγορία:	[EL] Φαρμακευτική[EN] Pharmacy and materia medica [EL] Κυτταρολογία[EN] Cytology [EL] Βιοχημεία[EN] Biochemistry [EL] Χημική Βιολογία[EN] Chemical Biology
Λέξεις-Κλειδιά:	Alzheimer's disease Behavior Frailty Proteasome Therapeutic Animals Disease Models, Animal Mice Mice, Transgenic Phenotype Proteasome Endopeptidase Complex Alzheimer Disease Amyloid beta-Peptides
Κάτοχος πνευματικών δικαιωμάτων:	Copyright © 2020 The Authors. Published by Elsevier Inc.
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.sciencedirect.com/science/article/pii/S0891584920316622?via%3Dihub
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://www.sciencedirect.com/journal/free-radical-biology-and-medicine
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο