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Proteostasis and Proteotoxicity in the Network Medicine Era

Authors
  • Lualdi, Marta
  • Alberio, Tiziana
  • Fasano, Mauro
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
Sep 03, 2020
Volume
21
Issue
17
Identifiers
DOI: 10.3390/ijms21176405
PMID: 32899160
PMCID: PMC7503343
Source
PubMed Central
Keywords
License
Green

Abstract

Neurodegenerative proteinopathies are complex diseases that share some pathogenetic processes. One of these is the failure of the proteostasis network (PN), which includes all components involved in the synthesis, folding, and degradation of proteins, thus leading to the aberrant accumulation of toxic protein aggregates in neurons. The single components that belong to the three main modules of the PN are highly interconnected and can be considered as part of a single giant network. Several pharmacological strategies have been proposed to ameliorate neurodegeneration by targeting PN components. Nevertheless, effective disease-modifying therapies are still lacking. In this review article, after a general description of the PN and its failure in proteinopathies, we will focus on the available pharmacological tools to target proteostasis. In this context, we will discuss the main advantages of systems-based pharmacology in contrast to the classical targeted approach, by focusing on network pharmacology as a strategy to innovate rational drug design.

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