AUTHOR=Llanos-González Emilio , Henares-Chavarino Ángel Andres , Pedrero-Prieto Cristina María , García-Carpintero Sonia , Frontiñán-Rubio Javier , Sancho-Bielsa Francisco Javier , Alcain Francisco Javier , Peinado Juan Ramón , Rabanal-Ruíz Yoana , Durán-Prado Mario 

TITLE=Interplay Between Mitochondrial Oxidative Disorders and Proteostasis in Alzheimer’s Disease

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 13 - 2019

YEAR=2020

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2019.01444

DOI=10.3389/fnins.2019.01444

ISSN=1662-453X

ABSTRACT=Although the basis of Alzheimer`s Disease (AD) aetiology remain unknown, oxidative stress has been recognized as a prodromal factor associated to its progression. Oxidative stress refers to an imbalance between oxidants and antioxidants systems, which usually consists in an overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that overwhelms the intrinsic antioxidant defences. Due to this increased production of ROS and RNS, several biological functions as glucose metabolism or synaptic activity are impaired. In AD, growing evidence link the ROS-mediated damages with molecular targets including mitochondrial dynamics and function, protein quality control system and autophagic pathways, affecting the proteostasis balance. In this scenario, oxidative stress should not only be considered as a major feature in the pathophysiology of AD but also a potential target to combat the progression of the disease. In this review, we will discuss the role of oxidative stress in mitochondrial dysfunction, proteins quality control systems and autophagy associated to AD and suggest innovative therapeutic strategies based on a better understanding of the role of oxidative stress and proteostasis.