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A Cell- and Tissue-Specific Weakness of the Protein Homeostasis System Underlies Brain Vulnerability to Protein Aggregation.

Published version
Peer-reviewed

Type

Article

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Authors

Kundra, Rishika 
Dobson, Christopher M 
Vendruscolo, Michele 

Abstract

The phenomenon of protein misfolding and aggregation is associated with a wide range of neurodegenerative conditions that cause progressive loss of function in specific regions of the human brain. To understand the causes of the selective cell and tissue vulnerability to the formation of these deposits, we analyzed the ability of different cell and tissue types to respond, in the absence of disease, to the presence of high levels of aggregation-prone proteins. By performing a transcriptional analysis, we found that the protein homeostasis system that regulates protein aggregation is weaker in neurons than in other cell types and in brain tissues than in other body tissues. These results suggest that the intrinsic level of regulation of protein aggregation in the healthy state is correlated with the selective vulnerability of cells and tissues to protein misfolding diseases.

Description

Keywords

Neuroscience, Molecular physiology, Transcriptomics

Journal Title

iScience

Conference Name

Journal ISSN

2589-0042

Volume Title

23

Publisher