Cross-talk between redox signalling and protein aggregation

Abstract

It is well established that both an increase in reactive oxygen species (ROS: i.e. O2•−, H2O2 and OH•), as well as protein aggregation, accompany ageing and proteinopathies such as Parkinson's and Alzheimer's disease. However, it is far from clear whether there is a causal relation between the two. This review describes how protein aggregation can be affected both by redox signalling (downstream of H2O2), as well as by ROS-induced damage, and aims to give an overview of the current knowledge of how redox signalling affects protein aggregation and vice versa. Redox signalling has been shown to play roles in almost every step of protein aggregation and amyloid formation, from aggregation initiation to the rapid oligomerization of large amyloids, which tend to be less toxic than oligomeric prefibrillar aggregates. We explore the hypothesis that age-associated elevated ROS production could be part of a redox signalling-dependent-stress response in an attempt to curb protein aggregation and minimize toxicity.

Redox regulation of the insulin signalling pathway

“…H 2 O 2 is formed from superoxide by the action of superoxide dismutase (SOD) enzymes [ 15 ]. H 2 O 2 can also be produced directly, for instance by xanthine oxidase in purine catabolism or by the endoplasmic reticulum oxidoreduction ERO1 during disulphide bond formation by the protein folding system [ 18 ].…”

Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples

“…Although its cumulative upregulation or prognostic values were not very high, we explored its potential as a therapeutic target. Thioredoxin is a small redox protein that plays an active role in keeping the intracellular compartment in a reduced state, which is important to prevent protein aggregation (51, 52). The thioredoxin system consists of three components namely thioredoxin, thioredoxin reductase, and the reducing agent nicotinamide adenine dinucleotide phosphate (NADPH).…”

NRF2 and Primary Cilia: An Emerging Partnership

“…In many of these diseases, a prominent role is played by redox, proteostatic and other kinds of cellular stress [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. Consistently, primary cilia and Hh signaling can respond to redox and other stress signals, and their function may also protect cells from such stresses [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ].…”