AUTHOR=Santarelli Stefania , Londero Chiara , Soldano Alessia , Candelaresi Carlotta , Todeschini Leonardo , Vernizzi Luisa , Bellosta Paola 

TITLE=Drosophila melanogaster as a model to study autophagy in neurodegenerative diseases induced by proteinopathies

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 17 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1082047

DOI=10.3389/fnins.2023.1082047

ISSN=1662-453X

ABSTRACT=Proteinopathies (PPs) are a large group of neurodegenerative diseases characterized by the presence of specific protein aggregates within/outside neurons, caused by mutations that lead to alterations in the structure of such proteins. The presence of aggregates not only hijacks the physiological function of the sequestered proteins but is also toxic to the cells. These effects are particularly evident in neuronal cells of the central nervous system (CNS), where protein misfolding is one the principal cause of toxicity leading to neuronal death. Autophagy is a key mechanism that controls elimination of misfolded proteins and alterations in this pathway, as well as in the ubiquitin-proteasome system (UPS), have been strongly associated with protein aggregation in neurodegenerative diseases. The use of animal models to genetically mimic proteinopathies is crucial to better understand the mechanisms underlying the role of autophagy in these diseases. Many crucial findings concerning the molecular and cellular events upstream and downstream of protein aggregates formation, come from works using Drosophila models for the relative diseases. Indeed, despite the physiological and morphological differences between the fly and human brain, most of the biochemical and molecular aspects regulating protein homeostasis, including autophagy, are conserved between the two species. In this review, we will give an overview of the most common proteinopathies highlighting the role of studies that used Drosophila as a model to understand the conserved mechanisms that link protein misfolding to autophagy and that helped to better understand these neurodegenerative diseases in humans.