TY  - JOUR
AU  - Mladenović, Aleksandra
AU  - Kapetanou, Marianna
AU  - Lončarević Vasiljković, Nataša
AU  - Todorović, Smilja
AU  - Athanasopoulou, Sofia
AU  - Jović, Milena
AU  - Prvulović, Milica
AU  - Taoufik, Era
AU  - Matsas, Rebecca
AU  - Kanazir, Selma
AU  - Gonos, Efstathios S.
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4074
AB  - 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.
PB  - Elsevier Inc.
T2  - Free Radical Biology and Medicine
T1  - Pharmacological intervention in a transgenic mouse model improves Alzheimer's-associated pathological phenotype: Involvement of proteasome activation
VL  - 162
DO  - 10.1016/j.freeradbiomed.2020.11.038
SP  - 88
EP  - 103
ER  - 

@article{
author = "Mladenović, Aleksandra and Kapetanou, Marianna and Lončarević Vasiljković, Nataša and Todorović, Smilja and Athanasopoulou, Sofia and Jović, Milena and Prvulović, Milica and Taoufik, Era and Matsas, Rebecca and Kanazir, Selma and Gonos, Efstathios S.",
year = "2021",
abstract = "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.",
publisher = "Elsevier Inc.",
journal = "Free Radical Biology and Medicine",
title = "Pharmacological intervention in a transgenic mouse model improves Alzheimer's-associated pathological phenotype: Involvement of proteasome activation",
volume = "162",
doi = "10.1016/j.freeradbiomed.2020.11.038",
pages = "88-103"
}

Mladenović, A., Kapetanou, M., Lončarević Vasiljković, N., Todorović, S., Athanasopoulou, S., Jović, M., Prvulović, M., Taoufik, E., Matsas, R., Kanazir, S.,& Gonos, E. S.. (2021). Pharmacological intervention in a transgenic mouse model improves Alzheimer's-associated pathological phenotype: Involvement of proteasome activation. in Free Radical Biology and Medicine
Elsevier Inc.., 162, 88-103.
https://doi.org/10.1016/j.freeradbiomed.2020.11.038

Mladenović A, Kapetanou M, Lončarević Vasiljković N, Todorović S, Athanasopoulou S, Jović M, Prvulović M, Taoufik E, Matsas R, Kanazir S, Gonos ES. Pharmacological intervention in a transgenic mouse model improves Alzheimer's-associated pathological phenotype: Involvement of proteasome activation. in Free Radical Biology and Medicine. 2021;162:88-103.
doi:10.1016/j.freeradbiomed.2020.11.038 .

Mladenović, Aleksandra, Kapetanou, Marianna, Lončarević Vasiljković, Nataša, Todorović, Smilja, Athanasopoulou, Sofia, Jović, Milena, Prvulović, Milica, Taoufik, Era, Matsas, Rebecca, Kanazir, Selma, Gonos, Efstathios S., "Pharmacological intervention in a transgenic mouse model improves Alzheimer's-associated pathological phenotype: Involvement of proteasome activation" in Free Radical Biology and Medicine, 162 (2021):88-103,
https://doi.org/10.1016/j.freeradbiomed.2020.11.038 . .