Protein aggregation in cell biology: An aggregomics perspective of health and disease.

Seminars in Cell & Developmental Biology
Dezerae CoxDanny M Hatters

Abstract

Maintaining protein homeostasis (proteostasis) is essential for cellular health and is governed by a network of quality control machinery comprising over 800 genes. When proteostasis becomes imbalanced, proteins can abnormally aggregate or become mislocalized. Inappropriate protein aggregation and proteostasis imbalance are two of the central pathological features of common neurodegenerative diseases including Alzheimer, Parkinson, Huntington, and motor neuron diseases. How aggregation contributes to the pathogenic mechanisms of disease remains incompletely understood. Here, we integrate some of the key and emerging ideas as to how protein aggregation relates to imbalanced proteostasis with an emphasis on Huntington disease as our area of main expertise. We propose the term "aggregomics" be coined in reference to how aggregation of particular proteins concomitantly influences the spatial organization and protein-protein interactions of the surrounding proteome. Meta-analysis of aggregated interactomes from various published datasets reveals chaperones and RNA-binding proteins are common components across various disease contexts. We conclude with an examination of therapeutic avenues targeting proteostasis mechanisms.

Citations

Aug 23, 2019·Science Translational Medicine·Christophe LechauveMitchell J Weiss
May 18, 2020·International Journal of Molecular Sciences·Paola RusminiAngelo Poletti
Jan 23, 2020·Proceedings of the National Academy of Sciences of the United States of America·Xiaojing SuiDanny M Hatters
Oct 1, 2021·Molecular Neurobiology·Ribhav MishraAmit Mishra

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